Artículos de revistas:

1

Messner, K. "Articular cartilage transplantation using precultivated cells". Der Orthopäde 28, n.º 1 (enero de 1999): 61–67. http://dx.doi.org/10.1007/pl00003551.

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Enomura, Masahiro, Soichiro Murata, Yuri Terado, Maiko Tanaka, Shinji Kobayashi, Takayoshi Oba, Shintaro Kagimoto et al. "Development of a Method for Scaffold-Free Elastic Cartilage Creation". International Journal of Molecular Sciences 21, n.º 22 (11 de noviembre de 2020): 8496. http://dx.doi.org/10.3390/ijms21228496.

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Microtia is a congenital aplasia of the auricular cartilage. Conventionally, autologous costal cartilage grafts are collected and shaped for transplantation. However, in this method, excessive invasion occurs due to limitations in the costal cartilage collection. Due to deformation over time after transplantation of the shaped graft, problems with long-term morphological maintenance exist. Additionally, the lack of elasticity with costal cartilage grafts is worth mentioning, as costal cartilage is a type of hyaline cartilage. Medical plastic materials have been transplanted as alternatives to costal cartilage, but transplant rejection and deformation over time are inevitable. It is imperative to create tissues for transplantation using cells of biological origin. Hence, cartilage tissues were developed using a biodegradable scaffold material. However, such materials suffer from transplant rejection and biodegradation, causing the transplanted cartilage tissue to deform due to a lack of elasticity. To address this problem, we established a method for creating elastic cartilage tissue for transplantation with autologous cells without using scaffold materials. Chondrocyte progenitor cells were collected from perichondrial tissue of the ear cartilage. By using a multilayer culture and a three-dimensional rotating suspension culture vessel system, we succeeded in creating scaffold-free elastic cartilage from cartilage progenitor cells.

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3

Lindahl, Anders. "From gristle to chondrocyte transplantation: treatment of cartilage injuries". Philosophical Transactions of the Royal Society B: Biological Sciences 370, n.º 1680 (19 de octubre de 2015): 20140369. http://dx.doi.org/10.1098/rstb.2014.0369.

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This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis.

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4

Le, Hanxiang, Weiguo Xu, Xiuli Zhuang, Fei Chang, Yinan Wang y Jianxun Ding. "Mesenchymal stem cells for cartilage regeneration". Journal of Tissue Engineering 11 (enero de 2020): 204173142094383. http://dx.doi.org/10.1177/2041731420943839.

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Cartilage injuries are typically caused by trauma, chronic overload, and autoimmune diseases. Owing to the avascular structure and low metabolic activities of chondrocytes, cartilage generally does not self-repair following an injury. Currently, clinical interventions for cartilage injuries include chondrocyte implantation, microfracture, and osteochondral transplantation. However, rather than restoring cartilage integrity, these methods only postpone further cartilage deterioration. Stem cell therapies, especially mesenchymal stem cell (MSCs) therapies, were found to be a feasible strategy in the treatment of cartilage injuries. MSCs can easily be isolated from mesenchymal tissue and be differentiated into chondrocytes with the support of chondrogenic factors or scaffolds to repair damaged cartilage tissue. In this review, we highlighted the full success of cartilage repair using MSCs, or MSCs in combination with chondrogenic factors and scaffolds, and predicted their pros and cons for prospective translation to clinical practice.

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5

Plánka, Ladislav, David Starý, Jana Hlučilová, Jiří Klíma, Josef Jančář, Leoš Křen, Jana Lorenzová et al. "Comparison of Preventive and Therapeutic Transplantations of Allogeneic Mesenchymal Stem Cells in Healing of the Distal Femoral Growth Plate Cartilage Defects in Miniature Pigs". Acta Veterinaria Brno 78, n.º 2 (2009): 293–302. http://dx.doi.org/10.2754/avb200978020293.

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The aim of the study was to verify whether there is a difference in the lengthwise growth of the femurs and in their angular deformity when comparing preventive vs. therapeutic transplantation of allogeneic mesenchymal stem cells (MSCs) to an iatrogenic defect in the distal physis of femur. Modified composite chitosan/collagen type I scaffold with MSCs was transplanted to an iatrogenically created defect of the growth cartilage in the lateral condyle of the left femur in 20 miniature male pigs. In Group A of animals (n = 10) allogeneic MSCs were transplanted immediately after creating the defect in the distal physis of femur (preventive transplantation). In Group B of animals (n = 10) the same defect of the growth cartilage was treated by transplantation of allogeneic MSCs four weeks after its creation (therapeutic transplantation), after the excision of the bone bridge that had formed in it. On average, left femurs with a damaged distal physis and preventively transplanted allogeneic MSCs (Group A) grew during 4 months from transplantation by 0.56 ± 0.44 cm more than right femurs without the transplantation of MSCs, whereas left femurs with physeal defects treated with a therapeutic transplantation of allogeneic MSCs (Group B) by 0.14 ± 0.72 cm only, compared to right femurs without transplanted MSCs. Four months after preventive transplantation of MSCs (Group A), valgus deformity of the distal part of left femur with the defect was 0.78 ± 0.82°; in the control group (right femur in the same animal without MSCs transplantation) it was 3.7 ± 0.82°. After therapeutic transplantation of MSCs (Group B) 0.6 ± 3.4°, in the control group (right femur in the same animal without MSCs transplantation) it was 2.1 ± 2.9°. In all the animals of Groups A and B, the presence of newly formed hyaline cartilage was confirmed histologically and immunohistochemically. In the distal physis of right femurs with an iatrogenic defect of the growth cartilage without the transplantation of MSCs (control) bone bridge was formed. Preventive transplantation of allogeneic MSCs into the defect of the distal growth zone of femur appears more suitable compared to the therapeutic transplantation, with regard to the more pronounced lengthwise bone growth. Differences found in the extent of valgus deformity were non-significant comparing preventive and therapeutic transplantations of MSCs.

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6

Rim, Yeri Alice, Yoojun Nam y Ji Hyeon Ju. "Application of Cord Blood and Cord Blood-Derived Induced Pluripotent Stem Cells for Cartilage Regeneration". Cell Transplantation 28, n.º 5 (25 de septiembre de 2018): 529–37. http://dx.doi.org/10.1177/0963689718794864.

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Regeneration of articular cartilage is of great interest in cartilage tissue engineering since articular cartilage has a low regenerative capacity. Due to the difficulty in obtaining healthy cartilage for transplantation, there is a need to develop an alternative and effective regeneration therapy to treat degenerative or damaged joint diseases. Stem cells including various adult stem cells and pluripotent stem cells are now actively used in tissue engineering. Here, we provide an overview of the current status of cord blood cells and induced pluripotent stem cells derived from these cells in cartilage regeneration. The abilities of these cells to undergo chondrogenic differentiation are also described. Finally, the technical challenges of articular cartilage regeneration and future directions are discussed.

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7

Bae, Jung Yoon, Kazuaki Matsumura, Shigeyuki Wakitani, Amu Kawaguchi, Sadami Tsutsumi y Suong-Hyu Hyon. "Beneficial Storage Effects of Epigallocatechin-3-O-Gallate on the Articular Cartilage of Rabbit Osteochondral Allografts". Cell Transplantation 18, n.º 5-6 (mayo de 2009): 505–12. http://dx.doi.org/10.1177/096368970901805-604.

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A fresh osteochondral allograft is one of the most effective treatments for cartilage defects of the knee. Despite the clinical success, fresh osteochondral allografts have great limitations in relation to the short storage time that cartilage tissues can be well-preserved. Fresh osteochondral grafts are generally stored in culture medium at 4°C. While the viability of articular cartilage stored in culture medium is significantly diminished within 1 week, appropriate serology testing to minimize the chances for the disease transmission requires a minimum of 2 weeks. (–)-Epigallocatechin-3- O-gallate (EGCG) has differential effects on the proliferation of cancer and normal cells, thus a cytotoxic effect on various cancer cells, but a cytopreservative effect on normal cells. Therefore, a storage solution containing EGCG might extend the storage duration of articular cartilages. Rabbit osteochondral allografts were performed with osteochondral grafts stored at 4°C in culture medium containing EGCG for 2 weeks and then the clinical effects were examined with macroscopic and histological assessment after 4 weeks. The cartilaginous structure of an osteochondral graft stored with EGCG was well-preserved with high cell viability and glycosaminoglycan (GAG) content of the extracellular matrix (ECM). After an osteochondral allograft, the implanted osteochondral grafts stored with EGCG also provided a significantly better retention of the articular cartilage with viability and metabolic activity. These data suggest that EGCG can be an effective storage agent that allows long-term preservation of articular cartilage under cold storage conditions.

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8

Moskalewski, S. y J. Malejczyk. "Bone formation following intrarenal transplantation of isolated murine chondrocytes: chondrocyte-bone cell transdifferentiation?" Development 107, n.º 3 (1 de noviembre de 1989): 473–80. http://dx.doi.org/10.1242/dev.107.3.473.

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Isolated syngeneic epiphyseal chondrocytes transplanted into a muscle formed cartilage in which matrix resorption and endochondral ossification began at the end of the second week after transplantation. After 56 days cartilage was converted into an ossicle. In 7-day-old intrarenal transplants, epiphyseal chondrocytes formed nodules of cartilage. In 10-day-old transplants, islands of bone appeared. Slight resorption of cartilage was first noted in 14-day-old transplants of chondrocytes. After eight weeks, transplants contained mainly bone. Intramuscularly transplanted rib chondrocytes formed cartilage which did not ossify. Nevertheless, bone islands appeared in intrarenal transplants of rib chondrocytes. Bone was not formed in allogeneic intrarenal transplants of epiphyseal or rib chondrocytes, but appeared in such transplants in animals immunosuppressed by anti-thymocyte serum and procarbazine. When spleen cells from animals immunized with allogeneic chondrocytes were transferred to immunosuppressed chondrocyte recipients two weeks after intrarenal chondrocyte transplantation, the majority of osteocytes in bone islands was dead. On the other hand, endochondral bone formed in intramuscular transplants of allogenic epiphyseal chondrocytes in immunosuppressed recipients was not damaged by sensitized spleen cells. This suggested that bone in 10- to 14-day-old intrarenal transplants of chondrocytes arose from injected cells and not by induction. To see whether bone was formed by chondrocytes or by some cells contaminating the chondrocyte suspension, the superficial layer of rib cartilage was removed by collagenase digestion and only more central chondrocytes were used for transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

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9

Cima, L. G., J. P. Vacanti, C. Vacanti, D. Ingber, D. Mooney y R. Langer. "Tissue Engineering by Cell Transplantation Using Degradable Polymer Substrates". Journal of Biomechanical Engineering 113, n.º 2 (1 de mayo de 1991): 143–51. http://dx.doi.org/10.1115/1.2891228.

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This paper reviews our research in developing novel matrices for cell transplantation using bioresorbable polymers. We focus on applications to liver and cartilage as paradigms for regeneration of metabolic and structural tissue, but review the approach in the context of cell transplantation as a whole. Important engineering issues in the design of successful devices are the surface chemistry and surface microstructure, which influence the ability of the cells to attach, grow, and function normally; the porosity and macroscopic dimensions, which affect the transport of nutrients to the implanted cells; the shape, which may be necessary for proper function in tissues like cartilage; and the choice of implantation site, which may be dictated by the total mass of the implant and which may influence the dimensions of the device by the available vascularity. Studies show that both liver and cartilage cells can be transplanted in small animals using this approach.

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10

Longo, Umile Giuseppe, Stefano Petrillo, Edoardo Franceschetti, Alessandra Berton, Nicola Maffulli y Vincenzo Denaro. "Stem Cells and Gene Therapy for Cartilage Repair". Stem Cells International 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/168385.

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Cartilage defects represent a common problem in orthopaedic practice. Predisposing factors include traumas, inflammatory conditions, and biomechanics alterations. Conservative management of cartilage defects often fails, and patients with this lesions may need surgical intervention. Several treatment strategies have been proposed, although only surgery has been proved to be predictably effective. Usually, in focal cartilage defects without a stable fibrocartilaginous repair tissue formed, surgeons try to promote a natural fibrocartilaginous response by using marrow stimulating techniques, such as microfracture, abrasion arthroplasty, and Pridie drilling, with the aim of reducing swelling and pain and improving joint function of the patients. These procedures have demonstrated to be clinically useful and are usually considered as first-line treatment for focal cartilage defects. However, fibrocartilage presents inferior mechanical and biochemical properties compared to normal hyaline articular cartilage, characterized by poor organization, significant amounts of collagen type I, and an increased susceptibility to injury, which ultimately leads to premature osteoarthritis (OA). Therefore, the aim of future therapeutic strategies for articular cartilage regeneration is to obtain a hyaline-like cartilage repair tissue by transplantation of tissues or cells. Further studies are required to clarify the role of gene therapy and mesenchimal stem cells for management of cartilage lesions.

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11

Yang, Guihua, Jiashen Shao, Jiachen Lin, Haixia Yang, Jing Jin, Chenxi Yu, Bo Shen et al. "Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Improves Cartilage Repair in a Rabbit Model". BioMed Research International 2021 (25 de febrero de 2021): 1–8. http://dx.doi.org/10.1155/2021/6380141.

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The aim of this study was to investigate the therapeutic efficacy and safety of transplanting human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in the treatment of cartilage injury. First, the articular cartilage defect model in rabbits was constructed. Then, the identified hUCB-MSCs and rabbit bone marrow stem cells (rBM-MSCs) were transplanted into the bone defect, respectively, and the cartilage repair effect was observed by hematoxylin-eosin (HE) staining and immunohistochemistry. Besides, the glycosaminoglycan (GAG) content and biomechanics of the restoration area were also evaluated. In our study, hUCB-MSCs and rBM-MSCs exhibited typical MSC characteristics, with positive expressions of CD73, CD105, and CD90 and negative for CD45, CD34, CD14, and HLA-DR. After the transplantation of hUCB-MSCs and rBM-MSCs, the overall quality of cartilage tissue was significantly improved, and the recipients did not show significant side effects in general. However, the expression of matrix metalloproteinase-13 (MMP-13) in the de novo tissues of the hUCB-MSCs and rBM-MSCs groups was both increased, indicating that the novel tissues may have some potential osteoarthritic changes. In conclusion, our results suggest the therapeutic effect of hUCB-MSCs transplantation in cartilage regeneration, providing a promising future in the clinical treatment of cartilage injury.

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12

Dang, Luong Huu, Yuan Tseng, How Tseng y Shih-Han Hung. "Partial Decellularization for Segmental Tracheal Scaffold Tissue Engineering: A Preliminary Study in Rabbits". Biomolecules 11, n.º 6 (10 de junio de 2021): 866. http://dx.doi.org/10.3390/biom11060866.

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In this study, we developed a new procedure for the rapid partial decellularization of the harvested trachea. Partial decellularization was performed using a combination of detergent and sonication to completely remove the epithelial layers outside of the cartilage ring. The post-decellularized tracheal segments were assessed with vital staining, which showed that the core cartilage cells remarkably remained intact while the cells outside of the cartilage were no longer viable. The ability of the decellularized tracheal segments to evade immune rejection was evaluated through heterotopic implantation of the segments into the chest muscle of rabbits without any immunosuppressive therapy, which demonstrated no evidence of severe rejection or tissue necrosis under H&E staining, as well as the mechanical stability under stress-pressure testing. Finally, orthotopic transplantation of partially decellularized trachea with no immunosuppression treatment resulted in 2 months of survival in two rabbits and one long-term survival (2 years) in one rabbit. Through evaluations of posttransplantation histology and endoscopy, we confirmed that our partial decellularization method could be a potential method of producing low-immunogenic cartilage scaffolds with viable, functional core cartilage cells that can achieve long-term survival after in vivo transplantation.

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13

Silva, Laís Meireles Costa, Mariá Andrade de Carvalho Rocha, Marllos Henrique Vieira Nunes, Brenda Lurian do Nascimento Medeiros, Yulla Klinger de Carvalho Leite, Huanna Waleska Soares Rodrigues, Marcelo Campos Rodrigues, Hermínio José da Rocha Neto, Maria Acelina Martins de Carvalho y Napoleão Martins Argôlo Neto. "Xenogeneic Mesenchymal Stem Cells in the Formation of Hyaline Cartilage in Osteochondral Goat Failure". Acta Scientiae Veterinariae 46, n.º 1 (16 de mayo de 2018): 10. http://dx.doi.org/10.22456/1679-9216.82560.

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Background: Osteochondral knee failures are among the most common causes of disability among the elderly human population and animal athletes. The xenogeneic transplantation of mesenchymal stem cells is a questionable therapeutic alternative that, despite the low expression of Major Histocompatibility Complex type II by these cells, still has relevantuncertainties about the safety and clinical efficacy. The main objective of the present study was to investigate whether the xenogeneic transplantation of mesenchymal stem cells induces hyaline cartilage formation, without histopathological evidence of rejection, in osteochondralfailures of goats.Materials, Methods & Results: Five female goats were used, submitted to three surgical osteocondral failures in the right knee, treated with xenogenic mesenchymal stem cells of dental pulp, xenogenic platelet-rich plasma and hemostatic sponge of hydrolyzed collagen, respectively. The lesions were evaluated after 60 days of treatment, aiming to identify thepresence of hyaline cartilage or fibrocartilage and the subchondral bone pattern (regenerated or disorganized). Transplantation of xenogenic mesenchymal stem cells induced predominant formation of hyaline cartilage (P < 0.05), with no histopathological evidence of inflammationwhen compared to the other treatments. Therapies with xenogeneic platelet-rich plasma and hemostatic sponge of hydrolyzed collagen induced greater formation of fibrocartilaginous cartilage, with no significant difference between them (P > 0.05). Macroscopically, the lesions of the stem cell treated group showed formation of firm repair tissue, opaque staining, integrated with adjacent cartilage and with the failure filling almost completely. The groups treated with PRP and hemostatic sponge of hydrolyzed collagen presented, on average, partial filling of the lesion, with irregular shape and darkened coloration.Discussion. The absence of macroscopic and histopathological evidences of an inflammatory process on the surface and in the internal portion of the osteochondral lesions treated with xenogeneic stem cells, probably due to the low expression of Major Histocompatibility Complex type II by these cells, which would theoretically induce low rejection response. Such observations are of great importance, since graft-versus- host disease syndrome is a serious condition, responsible for the low therapeutic efficacy with transplantation of cells or grafts in humans. The formation of fibrocartilage, although without macro and microscopic evidence of degeneration or necrosis, in the osteochondral failures treated with PRP and hemostatic collagen sponge suggest that paracrine factors of the local microenvironment of the osteochondral failure are possibly responsible for the formation of fibrocartilaginous tissue or by inhibition of normal cartilage formation. The fibrocartilage formed in the Plasmaand Control groups, contributed to the commitment in the filling of the lesion, contrasting with the almost complete fill of the lesions treated with stem cells. The xenotransplantation of mesenchymal stem cells induced formation of hyaline cartilage and did not promote histopathological evidence of rejection in osteochondral lesions of goat knees. The treatments with PRP and hemostatic sponge of hydrolyzed collagen induced greater formation of fibrocartilaginous cartilaginous surface in the osteochondral failures.

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14

Thorp, Hallie, Kyungsook Kim, Makoto Kondo, Travis Maak, David W. Grainger y Teruo Okano. "Trends in Articular Cartilage Tissue Engineering: 3D Mesenchymal Stem Cell Sheets as Candidates for Engineered Hyaline-Like Cartilage". Cells 10, n.º 3 (13 de marzo de 2021): 643. http://dx.doi.org/10.3390/cells10030643.

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Articular cartilage defects represent an inciting factor for future osteoarthritis (OA) and degenerative joint disease progression. Despite multiple clinically available therapies that succeed in providing short term pain reduction and restoration of limited mobility, current treatments do not reliably regenerate native hyaline cartilage or halt cartilage degeneration at these defect sites. Novel therapeutics aimed at addressing limitations of current clinical cartilage regeneration therapies increasingly focus on allogeneic cells, specifically mesenchymal stem cells (MSCs), as potent, banked, and available cell sources that express chondrogenic lineage commitment capabilities. Innovative tissue engineering approaches employing allogeneic MSCs aim to develop three-dimensional (3D), chondrogenically differentiated constructs for direct and immediate replacement of hyaline cartilage, improve local site tissue integration, and optimize treatment outcomes. Among emerging tissue engineering technologies, advancements in cell sheet tissue engineering offer promising capabilities for achieving both in vitro hyaline-like differentiation and effective transplantation, based on controlled 3D cellular interactions and retained cellular adhesion molecules. This review focuses on 3D MSC-based tissue engineering approaches for fabricating “ready-to-use” hyaline-like cartilage constructs for future rapid in vivo regenerative cartilage therapies. We highlight current approaches and future directions regarding development of MSC-derived cartilage therapies, emphasizing cell sheet tissue engineering, with specific focus on regulating 3D cellular interactions for controlled chondrogenic differentiation and post-differentiation transplantation capabilities.

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15

Chailakhyan, R. K., A. B. Shekhter, V. I. Tel’pukhov, S. V. Ivannikov, Yu V. Gerasimov, N. N. Vorobieva, I. L. Moskvina y V. N. Bagratashvili. "Repair of Partial Thickness Articular Hyaline Cartilage Injuries with Multipotent Mesenchymal Stromal Bone Marrow Cells Transplantation in Rabbits". N.N. Priorov Journal of Traumatology and Orthopedics 22, n.º 1 (15 de marzo de 2015): 23–27. http://dx.doi.org/10.17816/vto201522123-27.

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Possibility of hyaline cartilage integrity restoration using multipotent mesenchymal stromal cells (MMSC) was studied on the rabbit model of partial thickness articular hyaline cartilage defect without subchondral plate damage. Size of defect made up 0.5 cm in diameter and 1.5 mm deep. Autologous bone marrow was harvested from the resected upper flaring portion of the ilium, single cell suspension was prepared and cultured in matrasses. Grown MMSC were centrifuged and the sediment was transferred into the cartilage defect. The cells were covered with either vicryl or gelatin sponge, or vicryl mesh. Histologic examination was performed in 4 months. It was shown that the most active regeneration of hyaline cartilage tissue, that substituted the largest part of a defect, was noted when MMSC were covered with vicryl mesh. One of the advantages of vicryl mesh use was that it neither protruded above the cartilaginous plate nor compressed the cells, and slowly resolved.

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16

Chailakhyan, R. K., A. B. Shekhter, V. I. Tel’Pukhov, S. V. Ivannikov, Yu V. Gerasimov, N. N. Vorobieva, I. L. Moskvina y V. N. Bagratashvili. "Repair of Partial Thickness Articular Hyaline Cartilage Injuries with Multipotent Mesenchymal Stromal Bone Marrow Cells Transplantation in Rabbits". Vestnik travmatologii i ortopedii imeni N.N. Priorova, n.º 1 (30 de marzo de 2015): 23–27. http://dx.doi.org/10.32414/0869-8678-2015-1-23-27.

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Possibility of hyaline cartilage integrity restoration using multipotent mesenchymal stromal cells (MMSC) was studied on the rabbit model of partial thickness articular hyaline cartilage defect without subchondral plate damage. Size of defect made up 0.5 cm in diameter and 1.5 mm deep. Autologous bone marrow was harvested from the resected upper flaring portion of the ilium, single cell suspension was prepared and cultured in matrasses. Grown MMSC were centrifuged and the sediment was transferred into the cartilage defect. The cells were covered with either vicryl or gelatin sponge, or vicryl mesh. Histologic examination was performed in 4 months. It was shown that the most active regeneration of hyaline cartilage tissue, that substituted the largest part of a defect, was noted when MMSC were covered with vicryl mesh. One of the advantages of vicryl mesh use was that it neither protruded above the cartilaginous plate nor compressed the cells, and slowly resolved.

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17

Li, Bing Hui, Yong Yu y Dan Xu. "The Application of Tissue Engineering Cartilage and Bracket Constructed Biomaterials for Athletic Injury". Advanced Materials Research 643 (enero de 2013): 68–71. http://dx.doi.org/10.4028/www.scientific.net/amr.643.68.

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The development of tissue engineering techniques for cartilage repair and regeneration provided a new way, according to their own characteristics and structure of the cartilage, as artificial cartilage replacement materials and scaffold materials should have good biomechanical properties. The effect of autologous cartilage transplantation is best in the field of articular cartilage repair, the study of bone marrow stromal cells in vitro tests and animal experiments was more, and the clinical application was less, which is still in the stage of exploration. Biomaterials material for tissue repair plays a more and more important role, especially in athletic injury.

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18

Plánka, L., A. Nečas, P. Gál, H. Kecová, E. Filová, L. Křen y P. Krupa. "Prevention of Bone Bridge Formation Using Transplantation of the Autogenous Mesenchymal Stem Cells to Physeal Defects: An Experimental Study in Rabbits". Acta Veterinaria Brno 76, n.º 2 (2007): 253–63. http://dx.doi.org/10.2754/avb200776020253.

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Physeal cartilage is known to have poor self-repair capacity after injury. Evaluation of the ability of cultured mesenchymal stem cells to repair damaged physis is the topic of current research. In 10 immature New Zealand white rabbits autogenous mesenchymal stem cells were transplanted into a iatrogenic physeal defect in a lateral portion of the distal growth plate of the right femur. The same defect without stem cells transplantation in the left femoral distal physis served as a control. In our study, we used our own technique of implantation of MSCs with a newly modified gel scaffold (New Composite Hyaluronate/Collagen Type I/Fibrin Scaffold). The rabbits were euthanized 4 months after transplantation. Bone length discrepancy and valgus deformity were measured from femoral radiographs. Healing of the defect was investigated histologically. The ability of mesenchymal stem cells to survive and promote cartilage healing in the physeal defect was assessed by immunofluorescence. Average difference in femur length measured from surgery to euthanasia (4 months) was 0.61 ± 0.19 cm after preventive transplantation of MSCs in the right femur, but only 0.11 ± 0.07 cm in the left femur. Average angular (valgus) deformity of the right femur with MSCs preventively transplanted to iatrogenically damaged distal femoral physis was 1.2 ± 0.72 °. Valgus deformity in the left femur was 5.4 ± 2.5 °. Prophylactic transplantation of autogenous mesenchymal stem cells to iatrogenically damaged distal growth plate of the rabbit femur prevented a bone bridge formation and resulted in healing of the physeal defect with hyaline cartilage. Immunofluorescence examination showed that the chondrocytes newly formed in growth zone are the result of implanted MSCs differentiation. Femur growth in traumatized physis was maintained even after transplantation of autogenous MSCs. As compared with the opposite femur (with physeal defect but without transplanted MSCs), the bone showed no significant shortening or valgus deformity (p = 0.018).

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Wang, Qian, Na Yang, Kun Zhang, Zhong Li, Yangjun Zhu y Zhe Song. "Effect of intra-articular injection of adipose stem cells on traumatic osteoarthritis cartilage defects". Materials Express 11, n.º 1 (1 de enero de 2021): 28–37. http://dx.doi.org/10.1166/mex.2021.1874.

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Traumatic osteoarthritis with cartilage defects can lead to mobility problems. Mitotic activity in cartilage is extremely low, and once damaged, repairing can be difficult. The commonly used autologous or allogeneic cartilage transplantation techniques also have certain limitations. In recent years, directed induction of osteoblastic differentiation using adipocytes has been shown to be effective in repairing cartilage defects. However, it is often induced in vitro and is prone to incomplete or over-differentiation. In addition, because of the large differences in the in vivo and in vitro microenvironment, exploring the influence of these differences in the in vivo microenvironment on the directional differentiation of adipose-derived stem cells (ADSCs) and their effect on cartilage repair is necessary. In this study, a cartilage defect model in rabbits with traumatic osteoarthritis of the left knee was established, and different interventions were conducted in different groups. We determined the effect of directly injecting ADSCs into the joints on repairing cartilage defects in rabbits with traumatic osteoarthritis and analyzed the differences in repair time of newly developed cartilage defects and old cartilage frontal defects. The results indicated that the placement of a stent and injection of ADSCs improved the knee joint activity, increased the expression of BMP and TGF-β protein, and reduced the expression of inflammatory factors, including IL-1β, IL-6, IL-17, and TNF-α. No difference was found between the new cartilage defect and the old one. By directly observing the cartilage defect, intervention with ADSCs + scaffold increased the connection between the cartilage defect and the normal tissue and improved the cartilage repair effect. These results indicated that directly injecting ADSCs into the joints is an effective approach for repairing cartilage defects in traumatic osteoarthritis, and it was not affected by the age of the defect.

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Muñoz-Criado, Ignacio, Jose Meseguer-Ripolles, Maravillas Mellado-López, Ana Alastrue-Agudo, Richard J. Griffeth, Jerónimo Forteza-Vila, Ramón Cugat, Montserrat García y Victoria Moreno-Manzano. "Human Suprapatellar Fat Pad-Derived Mesenchymal Stem Cells Induce Chondrogenesis and Cartilage Repair in a Model of Severe Osteoarthritis". Stem Cells International 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/4758930.

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Cartilage degeneration is associated with degenerative bone and joint processes in severe osteoarthritis (OA). Spontaneous cartilage regeneration is extremely limited. Often the treatment consists of a partial or complete joint implant. Adipose-derived stem cell (ASC) transplantation has been shown to restore degenerated cartilage; however, regenerative differences of ASC would depend on the source of adipose tissue. The infra- and suprapatellar fat pads surrounding the knee offer a potential autologous source of ASC for patients after complete joint substitution. When infrapatellar- and suprapatellar-derived stromal vascular fractions (SVF) were compared, a significantly higher CD105 (+) population was found in the suprapatellar fat. In addition, the suprapatellar SVF exhibited increased numbers of colony formation units and a higher population doubling in culture compared to the infrapatellar fraction. Both the suprapatellar- and infrapatellar-derived ASC were differentiated in vitro into mature adipocytes, osteocytes, and chondrocytes. However, the suprapatellar-derived ASC showed higher osteogenic and chondrogenic efficiency. Suprapatellar-derived ASC transplantation in a severe OA mouse model significantly diminished the OA-associated knee inflammation and cartilage degenerative grade, significantly increasing the production of glycosaminoglycan and inducing endogenous chondrogenesis in comparison with the control group. Overall, suprapatellar-derived ASC offer a potential autologous regenerative treatment for patients with multiple degenerative OA.

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Ba, Kai, Xueqin Wei, Duan Ni, Na Li, Tianfeng Du, Xinbo Wang y Wenting Pan. "Chondrocyte Co-cultures with the Stromal Vascular Fraction of Adipose Tissue in Polyhydroxybutyrate/Poly-(hydroxybutyrate-co-hydroxyhexanoate) Scaffolds: Evaluation of Cartilage Repair in Rabbit". Cell Transplantation 28, n.º 11 (24 de julio de 2019): 1432–38. http://dx.doi.org/10.1177/0963689719861275.

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Chondral defects are challenging to repair because of the poor self-healing capacity of articular cartilage. The aim of this study was to compare and investigate the cartilage regeneration of stromal vascular fraction (SVF) cells and adipose-derived stem cells (ASCs) co-cultured with chondrocytes seeding on scaffolds composed of polyhydroxybutyrate (PHB)/poly-(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx). In this study, the cellular morphologies and proliferation capabilities on scaffolds were evaluated. Next, scaffolds with 1:1 co-culture of ASCs/SVF and chondrocytes were implanted into the full-thickness cartilage defects in rabbit knee for 10 weeks. Cells seeded on the scaffolds showed better adhesion, migration, and proliferation in vitro. Importantly, implantation with scaffolds with SVF and chondrocytes revealed more desirable in vivo healing outcomes. Our results illustrate a one-step surgical procedure for the regeneration of focal cartilage defects using a mixture of SVF from adipose tissue and uncultured chondrocytes.

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22

Oshima, Yasushi, Nobuyoshi Watanabe, Ken-ichi Matsuda, Shinro Takai, Mitsuhiro Kawata y Toshikazu Kubo. "Behavior of Transplanted Bone Marrow-derived GFP Mesenchymal Cells in Osteochondral Defect as a Simulation of Autologous Transplantation". Journal of Histochemistry & Cytochemistry 53, n.º 2 (febrero de 2005): 207–16. http://dx.doi.org/10.1369/jhc.4a6280.2005.

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To elucidate the behavior of autologously transplanted mesenchymal cells in osteochondral defects, we followed transplanted cells using green fluorescent protein (GFP) transgenic rats, in which all cells express GFP signals in their cytoplasm and nuclei as transplantation donors. Bone marrow-derived mesenchymal cells, which contain mesenchymal stem cells (MSCs), were obtained from transgenic rats. Then, dense mesenchymal cell masses created by hanging-drop culture were transplanted and fixed with fibrin glue into osteochondral defects of wild-type rats. At 24 weeks after surgery, the defects were repaired with hyaline-like cartilage and subchondral bone. GFP positive cells, indicating transplanted mesenchymal-derived cells, were observed in the regenerated tissues for 24 weeks although GFP positive cells decreased in number with time. Because GFP causes no immunological rejection and requires no chemicals for visualization, transplantation between transgenic and wild-type rats can be regarded as a simulation of autologous transplantation, and the survivability of transplanted cells are able to be followed easily and reliably. Thus, the behavior of transplanted mesenchymal cells was able to be elucidated in vivo by this strategy, and the results could be essential in future tissue engineering for the regeneration of osteochondral defects with original hyaline cartilage and subchondral bone.

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Kondo, Shimpei, Yusuke Nakagawa, Mitsuru Mizuno, Kenta Katagiri, Kunikazu Tsuji, Shinji Kiuchi, Hideo Ono, Takeshi Muneta, Hideyuki Koga y Ichiro Sekiya. "Transplantation of Aggregates of Autologous Synovial Mesenchymal Stem Cells for Treatment of Cartilage Defects in the Femoral Condyle and the Femoral Groove in Microminipigs". American Journal of Sports Medicine 47, n.º 10 (15 de julio de 2019): 2338–47. http://dx.doi.org/10.1177/0363546519859855.

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Background: Previous work has demonstrated that patients with cartilage defects of the knee benefit from arthroscopic transplantation of autologous synovial mesenchymal stem cells (MSCs) in terms of magnetic resonance imaging (MRI), qualitative histologic findings, and Lysholm score. However, the effectiveness was limited by the number of cells obtained, so large-sized defects (>500 mm2) were not investigated. The use of MSC aggregates may enable treatment of larger defects by increasing the number of MSCs adhering to the cartilage defect. Purpose: To investigate whether transplantation of aggregates of autologous synovial MSCs with 2-step surgery could promote articular cartilage regeneration in microminipig osteochondral defects. Study Design: Controlled laboratory study. Methods: Synovial MSCs derived from a microminipig were examined for in vitro colony-forming and multidifferentiation abilities. An aggregate of 250,000 synovial MSCs was formed with hanging drop culture, and 16 aggregates (for each defect) were implanted on both osteochondral defects (6 × 6 × 1.5 mm) created in the medial femoral condyle and femoral groove (MSC group). The defects in the contralateral knee were left empty (control group). The knee joints were evaluated at 4 and 12 weeks by macroscopic findings and histology. MRI T1rho mapping images were acquired at 12 weeks. For cell tracking, synovial MSCs were labeled with ferucarbotran before aggregate formation and were observed with MRI at 1 week. Results: Synovial MSCs showed in vitro colony-forming and multidifferentiation abilities. Regenerative cartilage formation was significantly better in the MSC group than in the control group, as indicated by International Cartilage Repair Society score (macro), modified Wakitani score (histology), and T1rho mapping (biochemical MRI) in the medial condyle at 12 weeks. Implanted cells, labeled with ferucarbotran, were observed in the osteochondral defects at 1 week with MRI. No significant difference was noted in the modified Wakitani score at 4 weeks in the medial condyle and at 4 and 12 weeks in the femoral groove. Conclusion: Transplantation of autologous synovial MSC aggregates promoted articular cartilage regeneration at the medial femoral condyle at 12 weeks in microminipigs. Clinical Relevance: Aggregates of autologous synovial MSCs could expand the indications for cartilage repair with synovial MSCs.

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Nguyen, Phuc Dang-Ngoc, Ngoc Bich Vu, Ha Thi-Ngan Le, Thuy Thi-Thanh Dao, Long Xuan Gia y Phuc Van Pham. "Engineered cartilage tissue from biodegradable Poly(ε-caprolactone) scaffold and human umbilical cord derived mesenchymal stem cells". Biomedical Research and Therapy 5, n.º 02 (26 de febrero de 2018): 2000–2012. http://dx.doi.org/10.15419/bmrat.v5i02.414.

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Introduction: Cartilage injury is the most common injury among orthopedic diseases. The predominant treatment for this condition is cartilage transplantation. Therefore, production of cartilage for treatment is an important strategy in regenerative medicine of cartilage to provide surgeons with an additional option for treatment of cartilage defects. This study aimed to produce in vitro engineered cartilage tissue by culturing and differentiating umbilical cord derived mesenchymal stem cells on biodegradable Poly(ε-caprolactone) (PCL) scaffold. Methods: Human umbilical cord derived mesenchymal stem cells (UCMSCs) were isolated and expanded according to previous published protocols. UCMSCs were labeled with CD90 APC‑conjugated monoclonal antibody (CD90-APC) and then seeded onto porous PCL scaffolds. Cell adhesion and proliferation on PCL scaffolds were evaluated based on the strength/signal of APC, MTT assays, and scanning electron microscopy (SEM). The chondrogenic differentiation of UCMSCs on scaffolds was detected by Alcian Blue and Safranin O staining. Results: The results showed that UCMSCs successfully adhered, proliferated and differentiated into chondroblasts and chondrocytes on PCL scaffolds. The chondrocyte scaffolds were positive for some markers of cartilage, as indicated by Alcian Blue and Safranin O staining. Conclusion: In conclusion, this study showed successful production of cartilage tissues from UCMSCs on PCL scaffolds.

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Rim, Yeri Alice, Yoojun Nam, Narae Park, Hyerin Jung, Kijun Lee, Jennifer Lee y Ji Hyeon Ju. "Chondrogenic Differentiation from Induced Pluripotent Stem Cells Using Non-Viral Minicircle Vectors". Cells 9, n.º 3 (1 de marzo de 2020): 582. http://dx.doi.org/10.3390/cells9030582.

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Human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently, chondrogenesis using human pluripotent stem cells (hiPSCs) is accomplished using human recombinant growth factors. Here, we differentiate hiPSCs into chondrogenic pellets using minicircle vectors. Minicircles are a non-viral gene delivery system that can produce growth factors without integration into the host genome. We generated minicircle vectors containing bone morphogenetic protein 2 (BMP2) and transforming growth factor beta 3 (TGFβ3) and delivered them to mesenchymal stem cell-like, hiPSC-derived outgrowth (OG) cells. Cell pellets generated using minicircle-transfected OG cells successfully differentiated into the chondrogenic lineage. The implanted minicircle-based chondrogenic pellets recovered the osteochondral defects in rat models. This work is a proof-of-concept study that describes the potential application of minicircle vectors in cartilage regeneration using hiPSCs.

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Jiang, L., A. Ma, L. Song, Y. Hu, H. Dun, P. Daloze, M. Zafarullah y H. Chen. "THE COMBINATION OF AUTOLOGOUS MESENCHYMAL STEM CELLS, ACELLULAR DERMAL MATRIX AND GROWTH FACTORS FOR CARTILAGE REGENERATION IN EXPERIMENTAL CARTILAGE DEFECT MODEL IN NONHUMAN PRIMATES". Transplantation Journal 90 (julio de 2010): 466. http://dx.doi.org/10.1097/00007890-201007272-00862.

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Tu, Vy Thi-Kieu, Ha Thi-Ngan Le, Xuan Hoang-Viet To, Phuc Dang-Ngoc Nguyen, Phat Duc Huynh, Thuan Minh Le y Ngoc Bich Vu. "Method for in vitro production of cartilage microtissues from scaffold-free spheroids composed of human adipose-derived stem cells". Biomedical Research and Therapy 7, n.º 4 (26 de abril de 2020): 3697–708. http://dx.doi.org/10.15419/bmrat.v7i4.597.

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Introduction: Cartilage damage is one of the injuries that is difficult for the human body to self-repair due to the avascular and completely mature tissue with only few stem or progenitor cells present. Recently, some studies showed that engineered cartilage tissues could be used to treat or improve this injury. This study aimed to produce the cartilage microtissues from the differentiation of scaffold-free spheroids composed of human adipose-derived stem cells. Methods: Human adipose-derived stem cells (ADSCs) were isolated and expanded following the previously published study. They were then cultured in the non-adherent condition to produce spheroids. The spheroids of the ADSCs were collected and induced into cartilage microtissues in the inducible medium for 21 days. The cartilage microtissue was characterized by some cartilage phenotype markers, including the accumulation of extracellular matrix proteins (aggrecan, glycosaminoglycan, and type II collagen), and the expression of certain genes specific to chondrocytes (Sox9, Col2, Col1, and Acan). Results: The results showed that the expression of chondrocyte-specific genes gradually increased during the 21 days of culture for differentiation. On day 21, the microtissues expressed aggrecan, glycosaminoglycan, and type II collagen proteins. Conclusion: This study demonstrated that cartilage microtissues could easily be produced from scaffold-free spheroids from ADSCs. Thus, cartilage microtissues can be produced in this manner for in vivo transplantation to promote cartilage regeneration, or to produce cartilage tissues for in vitro studies.

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Liu, Jun-wei, Yong-li Wu, Wei Wei, Yan-ling Zhang, Di Liu, Xiao-xiu Ma, Chun Li y Yu-yuan Ma. "Effect of Warm Acupuncture Combined with Bone Marrow Mesenchymal Stem Cells Transplantation on Cartilage Tissue in Rabbit Knee Osteoarthritis". Evidence-Based Complementary and Alternative Medicine 2021 (11 de agosto de 2021): 1–12. http://dx.doi.org/10.1155/2021/5523726.

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The current study was designed to investigate the effect and underlying mechanism of warm acupuncture combined with bone marrow mesenchymal stem cells (BMSC) transplantation on cartilage tissue injury in rabbit knee osteoarthritis (KOA). In the study, 50 rabbits were randomly divided into 5 groups: blank group, KOA group, warm acupuncture group, BMSCs group, and warm acupuncture combined with BMSCs group. After warm acupuncture combined with BMSCs, the Modified Lequesne MG knee joint assessment scale was used to evaluate the degree of knee joint behavior, the Taiping Peng method generally observed the histomorphology changes of KOA rabbit cartilage, and hematoxylin-eosin staining, safranin O green staining, and toluidine blue staining were conducted to evaluate the extent of cartilage tissue pathology. Furthermore, transmission electron microscopy and TUNEL staining were used to observe cell apoptosis, and immunohistochemistry and qPCR analysis were used to detect the expression of apoptosis-related proteins and mRNA. Results showed that administration of warm acupuncture combined with BMSCs recovered the joint function and significantly decreased Lequesne MG score. The degree of cartilage tissue pathological damage has been improved, cartilage ultrastructure degeneration has recovered, peripheral blood vessels have mild edema, blood supply has gradually recovered, and even small amounts of red blood cells have appeared. In addition, warm acupuncture combined with BMSCs treatment suppressed chondrocyte apoptosis in rabbits with knee osteoarthritis by reduced TUNEL-positive chondrocytes and simultaneously reversed the mRNA expression of Bax, Bcl-2, and Caspase-3. These results indicate that warm acupuncture combined with BMSCs transplantation has a potential protective effect on rabbit KOA, which may be mediated by inhibiting chondrocyte apoptosis.

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Phull, Abdul-Rehman, Seong-Hui Eo, Qamar Abbas, Madiha Ahmed y Song Ja Kim. "Applications of Chondrocyte-Based Cartilage Engineering: An Overview". BioMed Research International 2016 (2016): 1–17. http://dx.doi.org/10.1155/2016/1879837.

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Chondrocytes are the exclusive cells residing in cartilage and maintain the functionality of cartilage tissue. Series of biocomponents such as different growth factors, cytokines, and transcriptional factors regulate the mesenchymal stem cells (MSCs) differentiation to chondrocytes. The number of chondrocytes and dedifferentiation are the key limitations in subsequent clinical application of the chondrocytes. Different culture methods are being developed to overcome such issues. Using tissue engineering and cell based approaches, chondrocytes offer prominent therapeutic option specifically in orthopedics for cartilage repair and to treat ailments such as tracheal defects, facial reconstruction, and urinary incontinence. Matrix-assisted autologous chondrocyte transplantation/implantation is an improved version of traditional autologous chondrocyte transplantation (ACT) method. An increasing number of studies show the clinical significance of this technique for the chondral lesions treatment. Literature survey was carried out to address clinical and functional findings by using various ACT procedures. The current study was conducted to study the pharmacological significance and biomedical application of chondrocytes. Furthermore, it is inferred from the present study that long term follow-up studies are required to evaluate the potential of these methods and specific positive outcomes.

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Thompson, Seth D., Rajeswari Pichika, Richard L. Lieber, G. R. Scott Budinger y Mitra Lavasani. "Systemic Transplantation of Adult Multipotent Stem Cells Functionally Rejuvenates Aged Articular Cartilage". Aging and disease 12, n.º 3 (2021): 726. http://dx.doi.org/10.14336/ad.2020.1118.

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Hyc, Anna, Jacek Malejczyk, Anna Osiecka y Stanislaw Moskalewski. "Immunological Response against Allogeneic Chondrocytes Transplanted into Joint Surface Defects in Rats". Cell Transplantation 6, n.º 2 (marzo de 1997): 119–24. http://dx.doi.org/10.1177/096368979700600205.

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Rat chondrocytes isolated from the articular–epiphyseal cartilage complex were transplanted into defects prepared in articular cartilage and subchondral bone. Transplants were taken for examination after 3 and 8 wk. Cartilage formed by syngeneic chondrocytes did not evoke formation of infiltrations. Contrary to that, in the vicinity of cartilage produced by allogeneic chondrocytes numerous infiltrating cells were present and cartilage resorption could be observed. Cyclosporine-A (CsA) treatment of recipients of allogeneic chondrocytes only partially suppressed accumulation of infiltrating cells and matrix resorption. Antichondrocyte immune response of chondrocyte graft recipients was studied by evaluation of spleen mononuclear cells (SMC) stimulation in mixed splenocytechondrocyte cultures and by evaluation of antichondrocyte cytotoxic antibodies. No difference in stimulation of SMC from intact rats by syngeneic and allogeneic chondrocytes was observed. Stimulation by allogeneic chondrocytes was slightly but significantly higher in recipients of syngeneic grafts. SMC of allogenic chondrocyte recipients were strongly stimulated by allogeneic chondrocytes. This response was absent in recipients treated with CsA. Spontaneous antichondrocyte cytotoxic antibody activity was detected in intact rats and in recipients of syngeneic grafts. In recipients of allogeneic chondrocytes the antibody response against allogeneic chondrocytes was raised but was statistically not significant owing to the considerable variation in the level of spontaneously occurring antichondrocyte antibodies.

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Epperlein, H., D. Meulemans, M. Bronner-Fraser, H. Steinbeisser y M. A. Selleck. "Analysis of cranial neural crest migratory pathways in axolotl using cell markers and transplantation". Development 127, n.º 12 (15 de junio de 2000): 2751–61. http://dx.doi.org/10.1242/dev.127.12.2751.

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We have examined the ability of normal and heterotopically transplanted neural crest cells to migrate along cranial neural crest pathways in the axolotl using focal DiI injections and in situ hybridization with the neural crest marker, AP-2. DiI labeling demonstrates that cranial neural crest cells migrate as distinct streams along prescribed pathways to populate the maxillary and mandibular processes of the first branchial arch, the hyoid arch and gill arches 1–4, following migratory pathways similar to those observed in other vertebrates. Another neural crest marker, the transcription factor AP-2, is expressed by premigratory neural crest cells within the neural folds and migrating neural crest cells en route to and within the branchial arches. Rotations of the cranial neural folds suggest that premigratory neural crest cells are not committed to a specific branchial arch fate, but can compensate when displaced short distances from their targets by migrating to a new target arch. In contrast, when cells are displaced far from their original location, they appear unable to respond appropriately to their new milieu such that they fail to migrate or appear to migrate randomly. When trunk neural folds are grafted heterotopically into the head, trunk neural crest cells migrate in a highly disorganized fashion and fail to follow normal cranial neural crest pathways. Importantly, we find incorporation of some trunk cells into branchial arch cartilage despite the random nature of their migration. This is the first demonstration that trunk neural crest cells can form cartilage when transplanted to the head. Our results indicate that, although cranial and trunk neural crest cells have inherent differences in ability to recognize migratory pathways, trunk neural crest can differentiate into cranial cartilage when given proper instructive cues.

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Cegielski, Marek, Wojciech Dziewiszek, Maciej Zabel, Piotr Dzięgiel, Dariusz Iżycki, Maciej Zatoński y Marek Bochnia. "Experimental application of xenogenous antlerogenic cells in replacement of auricular cartilage in rabbits". Xenotransplantation 15, n.º 6 (noviembre de 2008): 374–83. http://dx.doi.org/10.1111/j.1399-3089.2008.00497.x.

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Xia, Peng, Xinwei Wang, Qi Wang, Xiaoju Wang, Qiang Lin, Kai Cheng y Xueping Li. "Low-Intensity Pulsed Ultrasound Promotes Autophagy-Mediated Migration of Mesenchymal Stem Cells and Cartilage Repair". Cell Transplantation 30 (1 de enero de 2021): 096368972098614. http://dx.doi.org/10.1177/0963689720986142.

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Mesenchymal stem cell (MSC) migration is promoted by low-intensity pulsed ultrasound (LIPUS), but its mechanism is unclear. Since autophagy is known to regulate cell migration, our study aimed to investigate if LIPUS promotes the migration of MSCs via autophagy regulation. We also aimed to investigate the effects of intra-articular injection of MSCs following LIPUS stimulation on osteoarthritis (OA) cartilage. For the in vitro study, rat bone marrow-derived MSCs were treated with an autophagy inhibitor or agonist, and then they were stimulated by LIPUS. Migration of MSCs was detected by transwell migration assays, and stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR4) protein levels were quantified. For the in vivo study, a rat knee OA model was generated and treated with LIPUS after an intra-articular injection of MSCs with autophagy inhibitor added. The cartilage repair was assessed by histopathological analysis and extracellular matrix protein expression. The in vitro results suggest that LIPUS increased the expression of SDF-1 and CXCR4, and it promoted MSC migration. These effects were inhibited and enhanced by autophagy inhibitor and agonist, respectively. The in vivo results demonstrate that LIPUS significantly enhanced the cartilage repair effects of MSCs on OA, but these effects were blocked by autophagy inhibitor. Our results suggest that the migration of MSCs was enhanced by LIPUS through the activation autophagy, and LIPUS improved the protective effect of MSCs on OA cartilage via autophagy regulation.

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Moskalewski, Stanislaw, Anna Hyc, Tomasz Grzela y Jacek Malejczyk. "Differences in Cartilage Formed Intramuscularly or in Joint Surface Defects by Syngeneic Rat Chondrocytes Isolated from the Articular-Epiphyseal Cartilage Complex". Cell Transplantation 2, n.º 6 (noviembre de 1993): 467–73. http://dx.doi.org/10.1177/096368979300200605.

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Syngeneic rat chondrocytes isolated from the articular-epiphyseal cartilage complex were suspended in hyaluronic acid and transplanted intramuscularly or into joint surface defects. Transplants were fixed in ruthenium hexammonium trichloride and embedded in glycol methacrylate. In cartilage nodules produced intramuscularly, chondrocyte hypertrophy and matrix calcification were observed after 2 wk. Partial ossification occurred after 4 wk and the cartilage was almost completely replaced by an ossicle after 8 wk. Only small, dispersed groups of chondrocytes remained within the ossicle. In cartilage formed in joint surface defects a superficial and a deep zone were distinguished. Chondrocytes in the superficial zone did not hypertrophy and cartilage remained unossified. In the deep zone matrix calcification and bone formation occurred. These processes were, however, retarded in comparison with intramuscular transplants. Thus, either intraarticular environment exerted an inhibitory effect on chondrocyte hypertrophy and matrix calcification or articular chondrocytes present among transplanted cells accumulated close to the joint lumen and reconstructed normal articular cartilage.

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Chen, Yu-Chun, Hwa-Chang Liu, Feng-Huei Lin y Chih-Hung Chang. "DEVELOPMENT OF ENGINEERED CARTILAGE PRODUCT FROM BONE MARROW MESENCHYMAL STEM CELLS: AN EXAMPLE IN TAIWAN". Journal of Musculoskeletal Research 24, n.º 01 (marzo de 2021): 2130001. http://dx.doi.org/10.1142/s0218957721300015.

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Cartilage can redistribute human body’s daily loads and decrease the friction force in the diarthrodial joints. However, it may be injured due to trauma, sports injury, biomechanical imbalance, and genetic disease. Microfracture (MF), osteochondral autograft transplantation (OAT), and autologous chondrocyte implantation (ACI) are the most common treatment procedures in the hospital. Recently, the concept of tissue engineering involving the combination of cells, scaffolds, and bioactive signals has inspired researchers. Our team of researchers synthesized a tri-copolymer from biological polymer by using gelatin, chondroitin-6-sulfate, and hyaluronic acid through cross-linking reaction. Lacuna formation could be seen in the tri-copolymer surrounding the chondrocytes, and some newly formed glycosaminoglycan was found in the engineered cartilage. Considering the dedifferentiation possibility of chondrocyte, bone marrow mesenchymal stem cells (BMSCs) become an ideal cell source for cartilage tissue regeneration, since they can be easily harvested from adult tissue, and be expanded in vitro. In an in-vivo porcine pilot study, the results showed that the defect site could be regenerated by BMSCs/collagen gel, and is formed with fibro/hyaline mixed cartilage tissue after implantation for six months. Several clinical studies using BMSCs for cartilage defect treatment were also conducted recently; clinical outcomes such as IKDC, Lysholm, and Tegner scores improved when the cartilage defects were repaired by several millions of mesenchymal stem cells, and there is no tumor formation after being treated with BMSCs during the 10-year follow-up. Moreover, recently a commercial BMSCs/collagen gel composite for cartilage repair was developed in Taiwan and clinical trial was conducted in 2008; the results showed that there is an improvement in IKDC and MRI scores during the nine-year follow-up. It seems that using an engineered cartilage made from BMSCs/collagen gel for cartilage defect treatment is a promising method.

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Choi, Woo Hee, Hwal Ran Kim, Su Jeong Lee, Nayoung Jeong, So Ra Park, Byung Hyune Choi y Byoung-Hyun Min. "Fetal Cartilage-Derived Cells Have Stem Cell Properties and Are a Highly Potent Cell Source for Cartilage Regeneration". Cell Transplantation 25, n.º 3 (marzo de 2016): 449–61. http://dx.doi.org/10.3727/096368915x688641.

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Ryu, Dong Jin, Yoon Sang Jeon, Jun Sung Park, Gi Cheol Bae, Jeong-seok Kim y Myung Ku Kim. "Comparison of Bone Marrow Aspirate Concentrate and Allogenic Human Umbilical Cord Blood Derived Mesenchymal Stem Cell Implantation on Chondral Defect of Knee: Assessment of Clinical and Magnetic Resonance Imaging Outcomes at 2-Year Follow-Up". Cell Transplantation 29 (1 de enero de 2020): 096368972094358. http://dx.doi.org/10.1177/0963689720943581.

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Biological repair of cartilage lesions remains a significant clinical challenge. A wide variety of methods involving mesenchymal stem cells (MSCs) have been introduced. Because of the limitation of the results, most of the treatment methods have not yet been approved by the Food and Drug Administration (FDA). However, bone marrow aspirate concentrate (BMAC) and human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) implantation were approved by Korea FDA. The aim of this study was to evaluate clinical and magnetic resonance imaging (MRI) outcomes after two different types of MSCs implantation in knee osteoarthritis. Fifty-two patients (52 knees) who underwent cartilage repair surgery using the BMAC (25 knees) and hUCB-MSCs (27 knees) were retrospectively evaluated for 2 years after surgery. Clinical outcomes were evaluated according to the score of visual analogue scale (VAS), the International Knee Documentation Committee (IKDC) subjective, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Cartilage repair was assessed according to the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and the International Cartilage Repair Society (ICRS) cartilage repair scoring system. At 2-year follow-up, clinical outcomes including VAS, IKDC, and KOOS significantly improved ( P < 0.05) in both groups; however, there were no differences between two groups. There was no significant difference in M-MOCART [1-year ( P = 0.261), 2-year ( P = 0.351)] and ICRS repair score ( P = 0.655) between two groups. Both groups showed satisfactory clinical and MRI outcomes. Implantation of MSCs from BMAC or hUCB-MSCs is safe and effective for repairing cartilage lesion. However, large cases and a well-controlled prospective design with long-term follow-up studies are needed.

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Miura, Yasushi y Shawn W. O'Driscoll. "Culturing Periosteum in Vitro: The Influence of Different Sizes of Explants". Cell Transplantation 7, n.º 5 (septiembre de 1998): 453–57. http://dx.doi.org/10.1177/096368979800700504.

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Periosteal transplantation is being used clinically to repair articular defects. Isolated cells and very small periosteal explants can be grown in tissue culture, but it will be necessary to test larger sizes for tissue engineering to be applied to clinical transplantation of periosteum. This study was conducted to assess the chondrogenic potential of different sizes of periosteal explants in agarose culture. Ninety-six rabbit tibial periosteal explants in three different sizes (small 1.5 × 2, medium 3 × 2, and large 4 × 6 mm, 32 pieces per size) were cultured in agarose suspension for 6 wk and given TGF-β1 (10 ng/mL) for the first 2 wk. Tissue growth, as indicated by normalized final wet weights of the explants after 6 wk in culture, was inversely proportional to explant size. Cartilage formation was observed in all explante. Histomorphometry revealed that cartilage formation was significantly better for the smaller explants (80% cartilage), but similar in the medium and larger explants (60% cartilage). Similar proportions of type II collagen were present in the different-sized explants. This study demonstrates that various sizes of periosteal explants can be grown in culture. Abundant cartilage was produced even by the large explants. © 1998 Elsevier Science Inc.

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Basok, Y. B., A. M. Grigoryev, L. A. Kirsanova, A. D. Kirillova, A. M. Subbot, A. V. Tsvetkova, E. A. Nemets y V. I. Sevastianov. "Comparative study of chondrogenesis of human adipose-derived mesenchymal stem cells when cultured in collagen-containing media under in vitro conditions". Russian Journal of Transplantology and Artificial Organs 23, n.º 3 (16 de septiembre de 2021): 90–100. http://dx.doi.org/10.15825/1995-1191-2021-3-90-100.

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In terms of method of production, collagen carriers are subdivided into materials obtained on the basis of extracellular matrix (ECM) components, particularly collagen-containing hydrogels and decellularized tissue.Objective: to compare in vitro the ability of biopolymer microheterogeneous collagen-containing hydrogel (BMCH) and tissue-specific matrix from decellularized porcine articular cartilage (DPAC) to support adhesion, proliferation and chondrogenic differentiation of human adipose-derived mesenchymal stem cells (hAMSCs).Materials and methods. For cartilage decellularization, we carried out treatment with surfactants (sodium dodecyl sulfate, Triton X-100) followed by exposure in DNAase. The metabolic activity of hAMSCs was assessed by PrestoBlue™ (Invitrogen, USA) staining. The morphological study of cell-engineered constructs (CECs) formed by culturing hAMSCs in the presence of matrices was performed using histological staining and scanning electron microscopy (SEM) with lanthanide contrasting.Results. The number of cells on the surface of both BMCH and DPAC increased within 14 days. Mitochondrial activity of the cells was 1.7, 1.7, and 1.3 times higher on days 3, 10, and 14 when cultured on DPAC compared to BMCH, respectively. On day 14 of cultivation in the chondrogenic culture medium, hAMSCs formed cell layers on the DPAC surface and on the BMCH surface. Cytoplasm of the cells included numerous granules, which, when stained, resembled the matrix itself. On the DPAC matrix surface, cells were more evenly distributed, whereas in the case of BMCH, cell adhesion and proliferation were observed only in certain areas. The ECM produced by the cells contained collagen and glycosaminoglycans (GAGs).Conclusion. The ability of DPAC obtained according to the developed protocol to form CECs with hAMSCs with uniform distribution of cells and their production of specific collagen- and GAG-containing ECM suggests that DPAC is effective in regeneration of damaged cartilage. Chondrogenic differentiation of hAMSCs was observed both when cultured with BMCH and with DPAC. When creating a tissue equivalent of cartilage in vitro, the advantage of using tissue-specific matrix over BMCH should be considered.

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Itokazu, Maki, Shigeyuki Wakitani, Hisashi Mera, Yoshihiro Tamamura, Yasushi Sato, Mutsumi Takagi y Hiroaki Nakamura. "Transplantation of Scaffold-Free Cartilage-Like Cell-Sheets Made from Human Bone Marrow Mesenchymal Stem Cells for Cartilage Repair". CARTILAGE 7, n.º 4 (23 de junio de 2016): 361–72. http://dx.doi.org/10.1177/1947603515627342.

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42

Jiang, Shuangpeng, Guangzhao Tian, Xu Li, Zhen Yang, Fuxin Wang, Zhuang Tian, Bo Huang et al. "Research Progress on Stem Cell Therapies for Articular Cartilage Regeneration". Stem Cells International 2021 (12 de febrero de 2021): 1–25. http://dx.doi.org/10.1155/2021/8882505.

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Injury of articular cartilage can cause osteoarthritis and seriously affect the physical and mental health of patients. Unfortunately, current surgical treatment techniques that are commonly used in the clinic cannot regenerate articular cartilage. Regenerative medicine involving stem cells has entered a new stage and is considered the most promising way to regenerate articular cartilage. In terms of theories on the mechanism, it was thought that stem cell-mediated articular cartilage regeneration was achieved through the directional differentiation of stem cells into chondrocytes. However, recent evidence has shown that the stem cell secretome plays an important role in biological processes such as the immune response, inflammation regulation, and drug delivery. At the same time, the stem cell secretome can effectively mediate the process of tissue regeneration. This new theory has attributed the therapeutic effect of stem cells to their paracrine effects. The application of stem cells is not limited to exogenous stem cell transplantation. Endogenous stem cell homing and in situ regeneration strategies have received extensive attention. The application of stem cell derivatives, such as conditioned media, extracellular vesicles, and extracellular matrix, is an extension of stem cell paracrine theory. On the other hand, stem cell pretreatment strategies have also shown promising therapeutic effects. This article will systematically review the latest developments in these areas, summarize challenges in articular cartilage regeneration strategies involving stem cells, and describe prospects for future development.

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Zhang, Rui, Qiaoxia Zhang, Zhiyu Zou, Zheng Li, Meng Jin, Jing An, Hui Li y Jianbing Ma. "Curcumin Supplementation Enhances Bone Marrow Mesenchymal Stem Cells to Promote the Anabolism of Articular Chondrocytes and Cartilage Repair". Cell Transplantation 30 (1 de enero de 2021): 096368972199377. http://dx.doi.org/10.1177/0963689721993776.

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Mesenchymal stem cells derived from bone marrows (BMSCs) and curcumin derived from turmeric were used for osteoarthritis (OA) treatment, respectively. We invested the effects of curcumin supplementation for BMSC therapeutic effects. In vitro, rat BMSCs were identified by dual-immunofluorescent staining of CD44 and CD90, and flow cytometry. Primary articular chondrocytes were identified by toluidine blue staining and immunofluorescent staining of Col2a1. EdU incorporation, migration assay, real-time quantitative polymerase chain reaction, and Western blot analyses were performed to evaluate the alterations of chondrocytes cocultured with BMSCs. In vivo, the rat model of OA was established by monoiodoacetic acid. After intra-articular injection of allogeneic BMSCs, articular cartilage damage and OA progression were evaluated by histological staining, and Osteoarthritis Research Society International and Mankin score evaluation. Although curcumin alone did not improve cell viability of primary articular chondrocytes, it promoted proliferation and migration of chondrocytes when cocultured with BMSCs. Meanwhile, the expression of anabolic genes in chondrocytes was remarkably increased both at mRNA and protein levels. In OA rats, curcumin and BMSCs cooperated to greatly promote articular cartilage repair and retard OA progression. Therefore, curcumin supplementation enhanced the BMSC function for the proliferation and migration of articular chondrocytes, and anabolic gene expression of extracellular matrix in articular chondrocytes in vitro, and the generation of articular cartilage in vivo. Our study shed light on the potential clinical application of curcumin cooperated with BMSCs in cartilage repair for OA treatment.

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Wu, Jiang, Guang Hui Wang, Hong Zhang, Yu Ping Wu, Yang Cheng Lv, Jing Song Liu, Jie Ke Ma y Jiang Zhu. "Chondrogenic Ability of Bone Marrow Mesenchymal Stem Cells in Alginate and Collagen Sponge". Key Engineering Materials 474-476 (abril de 2011): 1935–38. http://dx.doi.org/10.4028/www.scientific.net/kem.474-476.1935.

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In the present study, we have demonstrated that alginate and collagen sponge can act as scaffolds in order to support 3-dimensional structure for the differentiated bone marrow derived mesenchymal stem cells (BMSCs) during chondrogenesis in vitro and in vivo. The chondrogenic induced BMSCs were well distributed and differentiation in scaffolds system before implantation, then they produced sufficient ECM in the implants to form chondroid aggregates in vivo. In our opinion, well-differentiated BMSCs is a crucial feature of cartilage repair and only can be achieved in scaffold matrix. Furthermore, when dealing with cartilage defects, alginate seem to be superior to collagen sponge, and the combinational strategy of pre-induced BMSCs combined with alginate 3D-culture might be useful in improving conventional autologous cells transplantation or free-cells scaffolds.

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45

Kagimoto, Shintaro, Takanori Takebe, Shinji Kobayashi, Yuichiro Yabuki, Ayaka Hori, Koichi Hirotomi, Taro Mikami, Toshimasa Uemura, Jiro Maegawa y Hideki Taniguchi. "Autotransplantation of Monkey Ear Perichondrium-Derived Progenitor Cells for Cartilage Reconstruction". Cell Transplantation 25, n.º 5 (mayo de 2016): 951–62. http://dx.doi.org/10.3727/096368916x690917.

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46

Lu, Tsai-Jung, Fang-Yao Chiu, Hsiao-Ying Chiu, Ming-Chau Chang y Shih-Chieh Hung. "Chondrogenic Differentiation of Mesenchymal Stem Cells in Three-Dimensional Chitosan Film Culture". Cell Transplantation 26, n.º 3 (marzo de 2017): 417–27. http://dx.doi.org/10.3727/096368916x693464.

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Articular cartilage has a very limited capacity for self-repair, and mesenchymal stem cells (MSCs) have the potential to treat cartilage defects and osteoarthritis. However, in-depth mechanistic studies regarding their applications are required. Here we demonstrated the use of chitosan film culture for promoting chondrogenic differentiation of MSCs. We found that MSCs formed spheres 2 days after seeding on dishes coated with chitosan. When MSCs were induced in a chondrogenic induction medium on chitosan films, the size of the spheres continuously increased for up to 21 days. Alcian blue staining and immunohistochemistry demonstrated the expression of chondrogenic proteins, including aggrecan, type II collagen, and type X collagen at 14 and 21 days of differentiation. Importantly, chitosan, with a medium molecular weight (size: 190–310 kDa), was more suitable than other sizes for inducing chondrogenic differentiation of MSCs in terms of sphere size and expression of chondrogenic proteins and endochondral markers. We identified that the mechanistic target of rapamycin (mTOR) signaling and its downstream S6 kinase (S6K)/S6 were activated in chitosan film culture compared to that of monolayer culture. The activation of mTOR/S6K was continuously upregulated from days 2 to 7 of differentiation. Furthermore, we found that mTOR/S6K signaling was required for chondrogenic differentiation of MSCs in chitosan film culture through rapamycin treatment and mTOR knockdown. In conclusion, we showed the suitability of chitosan film culture for promoting chondrogenic differentiation of MSCs and its potential in the development of new strategies in cartilage tissue engineering.

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47

Liu, Jun-qi, Qi-wen Li y Zhen Tan. "New Insights on Properties and Spatial Distributions of Skeletal Stem Cells". Stem Cells International 2019 (3 de junio de 2019): 1–11. http://dx.doi.org/10.1155/2019/9026729.

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Skeletal stem cells (SSCs) are postnatal self-renewing, multipotent, and skeletal lineage-committed progenitors that are capable of giving rise to cartilage, bone, and bone marrow stroma including marrow adipocytes and stromal cells in vitro and in an exogenous environment after transplantation in vivo. Identifying and isolating defined SSCs as well as illuminating their spatiotemporal properties contribute to our understating of skeletal biology and pathology. In this review, we revisit skeletal stem cells identified most recently and systematically discuss their origin and distributions.

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48

Aoyama, H. y K. Asamoto. "Determination of somite cells: independence of cell differentiation and morphogenesis". Development 104, n.º 1 (1 de septiembre de 1988): 15–28. http://dx.doi.org/10.1242/dev.104.1.15.

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Somites are mesodermal structures which appear transiently in vertebrates in the course of their development. Cells situated ventromedially in a somite differentiate into the sclerotome, which gives rise to cartilage, while the other part of the somite differentiates into dermomyotome which gives rise to muscle and dermis. The sclerotome is further divided into a rostral half, where neural crest cells settle and motor nerves grow, and a caudal half. To find out when these axes are determined and how they rule later development, especially the morphogenesis of cartilage derived from the somites, we transplanted the newly formed three caudal somites of 2.5-day-old quail embryos into chick embryos of about the same age, with reversal of some axes. The results were summarized as follows. (1) When transplantation reversed only the dorsoventral axis, one day after the operation the two caudal somites gave rise to normal dermomyotomes and sclerotomes, while the most rostral somite gave rise to a sclerotome abnormally situated just beneath ectoderm. These results suggest that the dorsoventral axis was not determined when the somites were formed, but began to be determined about three hours after their formation. (2) When the transplantation reversed only the rostrocaudal axis, two days after the operation the rudiments of dorsal root ganglia were formed at the caudal (originally rostral) halves of the transplanted sclerotomes. The rostrocaudal axis of the somites had therefore been determined when the somites were formed. (3) When the transplantation reversed both the dorsoventral and the rostrocaudal axes, two days after the operation, sclerotomes derived from the prospective dermomyotomal region of the somites were shown to keep their original rostrocaudal axis, judging from the position of the rudiments of ganglia. Combined with results 1 and 2, this suggested that the fate of the sclerotomal cells along the rostrocaudal axis was determined previously and independently of the determination of somite cell differentiation into dermomyotome and sclerotome. (4) In the 9.5-day-old chimeric embryos with rostrocaudally reversed somites, the morphology of vertebrae and ribs derived from the explanted somites were reversed along the rostrocaudal axis. The morphology of cartilage derived from the somites was shown to be determined intrinsically in the somites by the time these were formed from the segmental plate. The rostrocaudal pattern of the vertebral column is therefore controlled by factors intrinsic to the somitic mesoderm, and not by interactions between this mesoderm and the notochord and/or neural tube, arising after segmentation.

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49

Gál, P., A. Nečas, L. Plánka, H. Kecová, L. Křen, P. Krupa, J. Hlučilová y D. Usvald. "Chondrocytic Potential of Allogenic Mesenchymal Stem Cells Transplanted without Immunosuppression to Regenerate Physeal Defect in Rabbits". Acta Veterinaria Brno 76, n.º 2 (2007): 265–75. http://dx.doi.org/10.2754/avb200776020265.

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Mesenchymal stem cells (MSCs) from bone marrow are multipotent cells capable of forming cartilage, bone, and other connective tissues. The objective of this study was to determine whether the use of allogenic mesenchymal stem cells could functionally heal a defect in the distal femoral physis in rabbits without the use of immunosuppressive therapy. A iatrogenic defect was created in the lateral femoral condyle of thirty-two New Zealand white rabbits, 7 weeks old, weighing 2.25 ± 0.24 kg. Each defect, 3.5 mm in width and 12 mm in length, in the right distal femoral physis was treated with allogenic mesenchymal stem cells in new composite hyaluronate/collagen type I/fibrin scaffold. The healing response was evaluated radiographically, by MRI (three weeks and four months after implantation) and also histologically, by Pearl’s reaction and with immunofluorescence (four months after implantation). The results were compared with the data for the control defects (without stem cell implantation) in left distal femoral physes. On average, right femurs with a damaged distal physis and transplanted MSCs grew more in length (0.55 ± 0.21 cm) compared with left femurs with a physeal defect without stem cell transplantation (0.46 ± 0.23 cm). Valgus deformity of right femurs with a physeal defect and transplanted MSCs was mild (0.2 ± 0.1 °). On the contrary, left femurs with a physeal defect without transplanted MSCs showed a significant valgus deformity (2.7 ± 1.6 °). For defects treated with allogenic mesenchymal stem cell implants, no adverse immune response and implant rejection were detected in this model. Histologically, no lymphocytic infiltration occurred. At four months after transplantation, hyaline cartilage had formed throughout the defects treated with allogenic MSCs. Labelled mesenchymal stem cells/differentiated chondrocytes were detected in the physeal defects based on magnetic resonance imaging and immunofluorescence. The results of this study demonstrated that allogenic mesenchymal stem cells in a new composite hyaluronate/collagen type I/fibrin scaffold repaired iatrogenic defects in the distal femoral physes in rabbits without the use of immunosuppressive therapy. The use of allogenic mesenchymal stem cells for the repair of physeal defects may be an alternative to autologous MSCs transplantation. An allogenic approach would enable mesenchymal stem cells to be isolated from any donor, providing a readily available source of cells for cartilage tissue repair.

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50

Salamone, Monica, Salvatrice Rigogliuso, Aldo Nicosia, Marcello Tagliavia, Simona Campora, Paolo Cinà, Carmelo Bruno y Giulio Ghersi. "Neural Crest-Derived Chondrocytes Isolation for Tissue Engineering in Regenerative Medicine". Cells 9, n.º 4 (14 de abril de 2020): 962. http://dx.doi.org/10.3390/cells9040962.

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Chondrocyte transplantation has been successfully tested and proposed as a clinical procedure aiming to repair articular cartilage defects. However, the isolation of chondrocytes and the optimization of the enzymatic digestion process, as well as their successful in vitro expansion, remain the main challenges in cartilage tissue engineering. In order to address these issues, we investigated the performance of recombinant collagenases in tissue dissociation assays with the aim of isolating chondrocytes from bovine nasal cartilage in order to establish the optimal enzyme blend to ensure the best outcomes of the overall procedure. We show, for the first time, that collagenase H activity alone is required for effective cartilage digestion, resulting in an improvement in the yield of viable cells. The extracted chondrocytes proved able to grow and activate differentiation/dedifferentiation programs, as assessed by morphological and gene expression analyses.

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