Статті в журналах: "Adipose-derived stem cells, regenerative medicine"

1

Gimble, Jeffrey M., Adam J. Katz, and Bruce A. Bunnell. "Adipose-Derived Stem Cells for Regenerative Medicine." Circulation Research 100, no. 9 (May 11, 2007): 1249–60. http://dx.doi.org/10.1161/01.res.0000265074.83288.09.

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Lina, Yani, and Andi Wijaya. "Adipose-Derived Stem Cells for Future Regenerative System Medicine." Indonesian Biomedical Journal 4, no. 2 (August 1, 2012): 59. http://dx.doi.org/10.18585/inabj.v4i2.164.

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BACKGROUND: The potential use of stem cell-based therapies for repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of disease. Despite the advances, the availability of stem cells remaining a challenge for both scientist and clinicians in pursuing regenerative medicine. CONTENT: Subcutaneous human adipose tissue is an abundant and accessible cell source for applications in tissue engineering and regenerative medicine. Routinely, the adipose issue is digested with collagenase or related lytic enzymes to release a heterogeneous population for stromal vascular fraction (SVF) cells. The SVF cells can be used directly or can be cultured in plastic ware for selection and expansion of an adherent population known as adipose-derived stromal/stem cells (ASCs). Their potential in the ability to differentiate into adipogenic, osteogenic, chondrogenic and other mesenchymal lineages, as well in their other clinically useful properties, includes stimulation of angiogenesis and suppression of inflammation.SUMMARY: Adipose tissue is now recognized as an accessible, abundant and reliable site for the isolation of adult stem cels suitable for the application of tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models.KEYWORDS: adipose tissue, adult stem cells, regenerative medicine, mesenchymal stem cells

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3

Skubis, Aleksandra, Bartosz Sikora, Nikola Zmarzły, Emilia Wojdas, and Urszula Mazurek. "Adipose-derived stem cells: a review of osteogenesis differentiation." Folia Biologica et Oecologica 12 (December 7, 2016): 38–47. http://dx.doi.org/10.1515/fobio-2016-0004.

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This review article provides an overview on adipose-derived stem cells (ADSCs) for implications in bone tissue regeneration. Firstly this article focuses on mesenchymal stem cells (MSCs) which are object of interest in regenerative medicine. Stem cells have unlimited potential for self-renewal and develop into various cell types. They are used for many therapies such as bone tissue regeneration. Adipose tissue is one of the main sources of mesenchymal stem cells (MSCs). Regenerative medicine intends to differentiate ADSC along specific lineage pathways to effect repair of damaged or failing organs. For further clinical applications it is necessary to understand mechanisms involved in ADSCs proliferation and differentiation. Second part of manuscript based on osteogenesis differentiation of stem cells. Bones are highly regenerative organs but there are still many problems with therapy of large bone defects. Sometimes there is necessary to make a replacement or expansion new bone tissue. Stem cells might be a good solution for this especially ADSCs which manage differentiate into osteoblast in in vitro and in vivo conditions.

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4

Frese, Laura, Petra E. Dijkman, and Simon P. Hoerstrup. "Adipose Tissue-Derived Stem Cells in Regenerative Medicine." Transfusion Medicine and Hemotherapy 43, no. 4 (2016): 268–74. http://dx.doi.org/10.1159/000448180.

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Konno, Masamitsu, Atsushi Hamabe, Shinichiro Hasegawa, Hisataka Ogawa, Takahito Fukusumi, Shimpei Nishikawa, Katsuya Ohta, et al. "Adipose-derived mesenchymal stem cells and regenerative medicine." Development, Growth & Differentiation 55, no. 3 (March 3, 2013): 309–18. http://dx.doi.org/10.1111/dgd.12049.

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6

Alt, Eckhard U., Glenn Winnier, Alexander Haenel, Ralf Rothoerl, Oender Solakoglu, Christopher Alt, and Christoph Schmitz. "Towards a Comprehensive Understanding of UA-ADRCs (Uncultured, Autologous, Fresh, Unmodified, Adipose Derived Regenerative Cells, Isolated at Point of Care) in Regenerative Medicine." Cells 9, no. 5 (April 29, 2020): 1097. http://dx.doi.org/10.3390/cells9051097.

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It has become practically impossible to survey the literature on cells derived from adipose tissue for regenerative medicine. The aim of this paper is to provide a comprehensive and translational understanding of the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) and its application in regenerative medicine. We provide profound basic and clinical evidence demonstrating that tissue regeneration with UA-ADRCs is safe and effective. ADRCs are neither ‘fat stem cells’ nor could they exclusively be isolated from adipose tissue. ADRCs contain the same adult stem cells ubiquitously present in the walls of blood vessels that are able to differentiate into cells of all three germ layers. Of note, the specific isolation procedure used has a significant impact on the number and viability of cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to specifically isolate and separate stem cells from the initial mixture of progenitor and stem cells found in ADRCs. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for more than minimally manipulating, stimulating and/or (genetically) reprogramming the cells for a broad range of clinical applications. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use as defined by the regulatory authorities.

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Sultanova, A. S., O. Ya Bespalova, and O. Yu Galkin. "Stromal-vascular fraction of adipose tissue as an alternative source of cellular material for regenerative medicine." Ukrainian Biochemical Journal 93, no. 1 (February 22, 2021): 40–50. http://dx.doi.org/10.15407/ubj93.01.040.

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Adipose tissue is the most convenient source of cellular material for regenerative medicine as it can be obtained in significant quantities via cosmetic liposuction, lipoaspiration of subcutaneous fat or by excision of fat deposits. Adipose tissue consists of adipocytes and cells, which are the part of the stromal-vascular fraction (SVF). Different cell populations can be isolated from SVF, among which the population of adipose tissue stem cells (adipose-derived stem cells, ADSC) is especially important for regenerative medicine. SVF can be obtained relatively easily from adipose tissue (adipose tissue is an alternative to bone marrow in terms of being a source of stem cells) and used to treat various pathologies. Recent studies show that SVF not only has a therapeutic effect similar to that of ADSC, but in some cases is even more effective. The article provides the analysis of the main methods of SVF obtainment, characteristics of SVF cellular composition, its potential for use in clinical medicine and its main advantages over other sources of cellular material, including ADSC cultured in vitro, for regenerative medicine. Keywords: adipocytes, adipose-derived stem cells, regenerative medicine, stromal-vascular fraction

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8

Levi, Benjamin, and Michael T. Longaker. "Concise Review: Adipose-Derived Stromal Cells for Skeletal Regenerative Medicine." STEM CELLS 29, no. 4 (April 2011): 576–82. http://dx.doi.org/10.1002/stem.612.

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9

Zuk, Patricia. "Adipose-Derived Stem Cells in Tissue Regeneration: A Review." ISRN Stem Cells 2013 (February 14, 2013): 1–35. http://dx.doi.org/10.1155/2013/713959.

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In 2001, researchers at the University of California, Los Angeles, described the isolation of a new population of adult stem cells from liposuctioned adipose tissue. These stem cells, now known as adipose-derived stem cells or ADSCs, have gone on to become one of the most popular adult stem cells populations in the fields of stem cell research and regenerative medicine. As of today, thousands of research and clinical articles have been published using ASCs, describing their possible pluripotency in vitro, their uses in regenerative animal models, and their application to the clinic. This paper outlines the progress made in the ASC field since their initial description in 2001, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo, their use in mediating inflammation and vascularization during tissue regeneration, and their potential for reprogramming into induced pluripotent cells.

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Yeh, Da-Chuan, Tzu-Min Chan, Horng-Jyh Harn, Tzyy-Wen Chiou, Hsin-Shui Chen, Zung-Sheng Lin, and Shinn-Zong Lin. "Adipose Tissue-Derived Stem Cells in Neural Regenerative Medicine." Cell Transplantation 24, no. 3 (March 2015): 487–92. http://dx.doi.org/10.3727/096368915x686940.

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11

Alió del Barrio, Jorge L., Ana De la Mata, María P. De Miguel, Francisco Arnalich-Montiel, Teresa Nieto-Miguel, Mona El Zarif, Marta Cadenas-Martín, et al. "Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells." Cells 11, no. 16 (August 16, 2022): 2549. http://dx.doi.org/10.3390/cells11162549.

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Adipose-derived stem cells are a subtype of mesenchymal stem cell that offers the important advantage of being easily obtained (in an autologous manner) from low invasive procedures, rendering a high number of multipotent stem cells with the potential to differentiate into several cellular lineages, to show immunomodulatory properties, and to promote tissue regeneration by a paracrine action through the secretion of extracellular vesicles containing trophic factors. This secretome is currently being investigated as a potential source for a cell-free based regenerative therapy for human tissues, which would significantly reduce the involved costs, risks and law regulations, allowing for a broader application in real clinical practice. In the current article, we will review the existing preclinical and human clinical evidence regarding the use of such adipose-derived mesenchymal stem cells for the regeneration of the three main layers of the human cornea: the epithelium (derived from the surface ectoderm), the stroma (derived from the neural crest mesenchyme), and the endothelium (derived from the neural crest cells).

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12

Sheykhhasan, Mohsen, Joanna K. L. Wong, and Alexander M. Seifalian. "Human Adipose-Derived Stem Cells with Great Therapeutic Potential." Current Stem Cell Research & Therapy 14, no. 7 (September 23, 2019): 532–48. http://dx.doi.org/10.2174/1574888x14666190411121528.

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: The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in regenerative medicine. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. While clinically, adipose-derived stem cells (ADSCs) are one of the most widely used types of stem cells used more than five years in clinically setting. It has many advantages including; yields a high number of ADSCs per volume of tissue, high rate of proliferation, anti-fibrotic, anti-apoptotic, anti-inflammation, immunomodulation, and paracrine mechanisms have been demonstrated in various preclinical studies. It is much easier to harvest compared with bone marrow stem cells. Results of clinical studies have demonstrated the potentials of ADSCs for stem cells therapy for a number of clinical disorders. The aim of this paper was to provide an update on the most recent developments of ADSCs, by highlighting the properties and features of ADSCs, critically discussing its clinical benefit and its clinical trials in treatment and regeneration. This is a multi-billion dollars industry with huge interest to clinician, academia and industries.

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Barba, Marta, Claudia Cicione, Camilla Bernardini, Fabrizio Michetti, and Wanda Lattanzi. "Adipose-Derived Mesenchymal Cells for Bone Regereneration: State of the Art." BioMed Research International 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/416391.

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Adipose tissue represents a hot topic in regenerative medicine because of the tissue source abundance, the relatively easy retrieval, and the inherent biological properties of mesenchymal stem cells residing in its stroma. Adipose-derived mesenchymal stem cells (ASCs) are indeed multipotent somatic stem cells exhibiting growth kinetics and plasticity, proved to induce efficient tissue regeneration in several biomedical applications. A defined consensus for their isolation, classification, and characterization has been very recently achieved. In particular, bone tissue reconstruction and regeneration based on ASCs has emerged as a promising approach to restore structure and function of bone compromised by injury or disease. ASCs have been used in combination with osteoinductive biomaterial and/or osteogenic molecules, in either static or dynamic culture systems, to improve bone regeneration in several animal models. To date, few clinical trials on ASC-based bone reconstruction have been concluded and proved effective. The aim of this review is to dissect the state of the art on ASC use in bone regenerative applications in the attempt to provide a comprehensive coverage of the topics, from the basic laboratory to recent clinical applications.

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14

Nagata, Tokuichiro, Tomoyuki Mitsumori, and Hideki Iwaguro. "Adipose tissue-derived stem and regenerative cells for tissue regeneration." Journal of Oral Biosciences 55, no. 3 (August 2013): 127–31. http://dx.doi.org/10.1016/j.job.2013.06.005.

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15

Bunnell, Bruce A. "Adipose Tissue-Derived Mesenchymal Stem Cells." Cells 10, no. 12 (December 6, 2021): 3433. http://dx.doi.org/10.3390/cells10123433.

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The long-held belief about adipose tissue was that it was relatively inert in terms of biological activity. It was believed that its primary role was energy storage; however, that was shattered with the discovery of adipokines. Scientists interested in regenerative medicine then reported that adipose tissue is rich in adult stromal/stem cells. Following these initial reports, adipose stem cells (ASCs) rapidly garnered interest for use as potential cellular therapies. The primary advantages of ASCs compared to other mesenchymal stem cells (MSCs) include the abundance of the tissue source for isolation, the ease of methodologies for tissue collection and cell isolation, and their therapeutic potential. Studies conducted both in vitro and in vivo have demonstrated that ASCs are multipotent, possessing the ability to differentiate into cells of mesodermal origins, including adipocytes, chondrocytes, osteoblast and others. Moreover, ASCs produce a broad array of cytokines, growth factors, nucleic acids (miRNAs), and other macromolecules into the surrounding milieu by secretion or in the context of microvesicles. The secretome of ASCs has been shown to alter tissue biology, stimulate tissue-resident stem cells, change immune cell activity, and mediate therapeutic outcomes. The quality of ASCs is subject to donor-to-donor variation driven by age, body mass index, disease status and possibly gender and ethnicity. This review discusses adipose stromal/stem cell action mechanisms and their potential utility as cellular therapeutics.

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Bahmad, Hisham F., Reem Daouk, Joseph Azar, Jiranuwat Sapudom, Jeremy C. M. Teo, Wassim Abou-Kheir, and Mohamed Al-Sayegh. "Modeling Adipogenesis: Current and Future Perspective." Cells 9, no. 10 (October 20, 2020): 2326. http://dx.doi.org/10.3390/cells9102326.

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Adipose tissue is contemplated as a dynamic organ that plays key roles in the human body. Adipogenesis is the process by which adipocytes develop from adipose-derived stem cells to form the adipose tissue. Adipose-derived stem cells’ differentiation serves well beyond the simple goal of producing new adipocytes. Indeed, with the current immense biotechnological advances, the most critical role of adipose-derived stem cells remains their tremendous potential in the field of regenerative medicine. This review focuses on examining the physiological importance of adipogenesis, the current approaches that are employed to model this tightly controlled phenomenon, and the crucial role of adipogenesis in elucidating the pathophysiology and potential treatment modalities of human diseases. The future of adipogenesis is centered around its crucial role in regenerative and personalized medicine.

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Kornicka, Katarzyna, Florian Geburek, Michael Röcken, and Krzysztof Marycz. "Stem Cells in Equine Veterinary Practice—Current Trends, Risks, and Perspectives." Journal of Clinical Medicine 8, no. 5 (May 14, 2019): 675. http://dx.doi.org/10.3390/jcm8050675.

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With this Editorial, we introduce the Special Issue “Adipose-Derived Stem Cells and Their Extracellular Microvesicles (ExMVs) for Tissue Engineering and Regenerative Medicine Applications” to the scientific community. In this issue, we focus on regenerative medicine, stem cells, and their clinical application.

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Surowiecka, Agnieszka, and Jerzy Strużyna. "Adipose-Derived Stem Cells for Facial Rejuvenation." Journal of Personalized Medicine 12, no. 1 (January 16, 2022): 117. http://dx.doi.org/10.3390/jpm12010117.

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The interest in regenerative medicine is increasing, and it is a dynamically developing branch of aesthetic surgery. Biocompatible and autologous-derived products such as platelet-rich plasma or adult mesenchymal stem cells are often used for aesthetic purposes. Their application originates from wound healing and orthopaedics. Adipose-derived stem cells are a powerful agent in skin rejuvenation. They secrete growth factors and anti-inflammatory cytokines, stimulate tissue regeneration by promoting the secretion of extracellular proteins and secrete antioxidants that neutralize free radicals. In an office procedure, without cell incubation and counting, the obtained product is stromal vascular fraction, which consists of not only stem cells but also other numerous active cells such as pericytes, preadipocytes, immune cells, and extra-cellular matrix. Adipose-derived stem cells, when injected into dermis, improved skin density and overall skin appearance, and increased skin hydration and number of capillary vessels. The main limitation of mesenchymal stem cell transfers is the survival of the graft. The final outcomes are dependent on many factors, including the age of the patient, technique of fat tissue harvesting, technique of lipoaspirate preparation, and technique of fat graft injection. It is very difficult to compare available studies because of the differences and multitude of techniques used. Fat harvesting is associated with potentially life-threatening complications, such as massive bleeding, embolism, or clots. However, most of the side effects are mild and transient: primarily hematomas, oedema, and mild pain. Mesenchymal stem cells that do not proliferate when injected into dermis promote neoangiogenesis, that is why respectful caution should be taken in the case of oncologic patients. A longer clinical observation on a higher number of participants should be performed to develop reliable indications and guidelines for transferring ADSCs.

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Dai, Ru, Zongjie Wang, Roya Samanipour, Kyo-in Koo, and Keekyoung Kim. "Adipose-Derived Stem Cells for Tissue Engineering and Regenerative Medicine Applications." Stem Cells International 2016 (2016): 1–19. http://dx.doi.org/10.1155/2016/6737345.

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Adipose-derived stem cells (ASCs) are a mesenchymal stem cell source with properties of self-renewal and multipotential differentiation. Compared to bone marrow-derived stem cells (BMSCs), ASCs can be derived from more sources and are harvested more easily. Three-dimensional (3D) tissue engineering scaffolds are better able to mimic thein vivocellular microenvironment, which benefits the localization, attachment, proliferation, and differentiation of ASCs. Therefore, tissue-engineered ASCs are recognized as an attractive substitute for tissue and organ transplantation. In this paper, we review the characteristics of ASCs, as well as the biomaterials and tissue engineering methods used to proliferate and differentiate ASCs in a 3D environment. Clinical applications of tissue-engineered ASCs are also discussed to reveal the potential and feasibility of using tissue-engineered ASCs in regenerative medicine.

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de Villiers, Jennifer Anne, Nicolette Houreld, and Heidi Abrahamse. "Adipose Derived Stem Cells and Smooth Muscle Cells: Implications for Regenerative Medicine." Stem Cell Reviews and Reports 5, no. 3 (August 11, 2009): 256–65. http://dx.doi.org/10.1007/s12015-009-9084-y.

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Sandiarini-Kamayana, Jenisa. "The use of adipose-derived stem cells in cell assisted lipotransfer as potential regenerative therapy in breast reconstruction." Scripta Medica 53, no. 2 (2022): 158–64. http://dx.doi.org/10.5937/scriptamed53-36491.

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Breast reconstruction for breast cancer patients is performed as a standard of care to improve patients' quality of life, physical and psychosocial well-being. Stem cell therapy holds a promise in regenerative medicine, including in breast reconstruction. This review explores the potential use of adipose-derived stem cells (ADSCs) in cell assisted lipotransfer (CAL) for reconstruction of the breast. The review of literature was done using electronic databases using appropriate keywords, including "adipose-derived stem cell", "stem cell therapy", "adipose-derived stem cell", "cell-assisted lipotransfer", "regenerative therapy", "breast cancer" and "breast reconstruction", with literatures limited to ten years post publication. Adipose-derived stem cells are multipotent cells with angiogenic and immunomodulatory potential. Several studies reveal ADSCs use in CAL results in long-term breast volume retention suggesting improved fat graft survival. Some conflicting outcomes are also discussed, potentially related to numbers of cells enriched and factors affecting the cells' microenvironment. The use of ADSCs in CAL may be beneficial for therapy of breast reconstruction in breast cancer patients after surgical management. Further investigation would be needed to improve the confidence of its clinical use.

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Jeanne Adiwinata Pawitan. "Prospect of Adipose Tissue Derived Mesenchymal Stem Cells in Regenerative Medicine." Cell & Tissue Transplantation & Therapy 2 (2009): 7–9. http://dx.doi.org/10.4137/cttt.s3654.

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M. Gimble, Jeffrey, and Mark E. Nuttall. "Adipose-Derived Stromal/Stem Cells (ASC) in Regenerative Medicine: Pharmaceutical Applications." Current Pharmaceutical Design 17, no. 4 (February 1, 2011): 332–39. http://dx.doi.org/10.2174/138161211795164220.

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Hoke, N., F. Salloum, K. Loesser-Casey, and Rakesh Kukreja. "Cardiac regenerative potential of adipose tissue-derived stem cells." Acta Physiologica Hungarica 96, no. 3 (September 2009): 251–65. http://dx.doi.org/10.1556/aphysiol.96.2009.3.1.

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Musa, Mutali, Marco Zeppieri, Ehimare S. Enaholo, Carlo Salati, and Pier Camillo Parodi. "Adipose Stem Cells in Modern-Day Ophthalmology." Clinics and Practice 13, no. 1 (February 4, 2023): 230–45. http://dx.doi.org/10.3390/clinpract13010021.

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Stem cells (SCs) have evolved as an interesting and viable factor in ophthalmologic patient care in the past decades. SCs have been classified as either embryonic, mesenchymal, tissue-specific, or induced pluripotent cells. Multiple novel management techniques and clinical trials have been established to date. While available publications are predominantly animal-model-based, significant material is derived from human studies and case-selected scenarios. This possibility of explanting cells from viable tissue to regenerate/repair damaged tissue points to an exciting future of therapeutic options in all fields of medicine, and ophthalmology is surely not left out. Adipose tissue obtained from lipo-aspirates has been shown to produce mesenchymal SCs that are potentially useful in different body parts, including the oculo-visual system. An overview of the anatomy, physiology, and extraction process for adipose-tissue-derived stem cells (ADSC) is important for better understanding the potential therapeutic benefits. This review examines published data on ADSCs in immune-modulatory, therapeutic, and regenerative treatments. We also look at the future of ADSC applications for ophthalmic patient care. The adverse effects of this relatively novel therapy are also discussed.

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Mizuno, Hiroshi, Morikuni Tobita, and A. Cagri Uysal. "Concise Review: Adipose-Derived Stem Cells as a Novel Tool for Future Regenerative Medicine." STEM CELLS 30, no. 5 (April 9, 2012): 804–10. http://dx.doi.org/10.1002/stem.1076.

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He, Xiang, Julei Zhang, Liang Luo, Jihong Shi, and Dahai Hu. "New Progress of Adipose-derived Stem Cells in the Therapy of Hypertrophic Scars." Current Stem Cell Research & Therapy 15, no. 1 (March 19, 2020): 77–85. http://dx.doi.org/10.2174/1574888x14666190904125800.

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Burns are a global public health issue of great concern. The formation of scars after burns and physical dysfunction of patients remain major challenges in the treatment of scars. Regenerative medicine based on cell therapy has become a hot topic in this century. Adipose-derived stem cells (ADSCs) play an important role in cellular therapy and have become a promising source of regenerative medicine and wound repair transplantation. However, the anti-scarring mechanism of ADSCs is still unclear yet. With the widespread application of ADSCs in medical, we firmly believe that it will bring great benefits to patients with hypertrophic scars.

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Geßner, Alec, Benjamin Koch, Kevin Klann, Dominik C. Fuhrmann, Samira Farmand, Ralf Schubert, Christian Münch, Helmut Geiger, and Patrick C. Baer. "Characterization of Extracellular Vesicles from Preconditioned Human Adipose-Derived Stromal/Stem Cells." International Journal of Molecular Sciences 22, no. 6 (March 12, 2021): 2873. http://dx.doi.org/10.3390/ijms22062873.

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Cell-free therapy using extracellular vesicles (EVs) from adipose-derived mesenchymal stromal/stem cells (ASCs) seems to be a safe and effective therapeutic option to support tissue and organ regeneration. The application of EVs requires particles with a maximum regenerative capability and hypoxic culture conditions as an in vitro preconditioning regimen has been shown to alter the molecular composition of released EVs. Nevertheless, the EV cargo after hypoxic preconditioning has not yet been comprehensively examined. The aim of the present study was the characterization of EVs from hypoxic preconditioned ASCs. We investigated the EV proteome and their effects on renal tubular epithelial cells in vitro. While no effect of hypoxia was observed on the number of released EVs and their protein content, the cargo of the proteins was altered. Proteomic analysis showed 41 increased or decreased proteins, 11 in a statistically significant manner. Furthermore, the uptake of EVs in epithelial cells and a positive effect on oxidative stress in vitro were observed. In conclusion, culture of ASCs under hypoxic conditions was demonstrated to be a promising in vitro preconditioning regimen, which alters the protein cargo and increases the anti-oxidative potential of EVs. These properties may provide new potential therapeutic options for regenerative medicine.

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Matsumoto, Goichi. "Fundamental research for jawbone regenerative medicine development using adipose tissue-derived stem cells." Impact 2021, no. 5 (June 7, 2021): 34–36. http://dx.doi.org/10.21820/23987073.2021.5.34.

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Bone loss around the teeth and jaw can occur for a number of reasons and this can lead to deterioration of the alveolar and masticatory and aesthetic disorders. Oftentimes, this impairs quality of life. It is possible to reconstruct the lower jaw using bone harvested from the patient's body but there are limitations associated with this method. Another option is using bone marrow cancellous bone fragments containing autologous bone marrow-derived somatic stem cells (BMSCs) but, again, there are limitations. Therefore, alternative methods of jawbone reconstruction are required. Dr Goichi Matsumoto, Department of Oral and Maxillofacial Surgery, Kanazawa Medical University, Japan, is an expert in this area. He is exploring the potential of using adipose tissue-derived stem cells (ADSCs) in jawbone reconstruction and believes this would overcome the limitations of existing methods as well as advancing regeneration therapy. There are numerous benefits to the use of ADSCs, but in order to move forward with this it is first necessary to explore the characteristics of ADSCs in detail, this includes investigating 'the proliferation ability and multi-differentiation potential of ADSCs. This will enable high-quantity and quality ADSCs to be obtained for clinical cell-based therapy and tissue engineering. It is Matsumoto's goal to develop a new mandibular regeneration treatment that involves regenerating the mandible by locally releasing a growth factor with bone-forming ability called basic fibroblast growth factor (bFGF). The researchers are also working to develop and commercialise a hybrid bone cement.

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Rothoerl, Ralf, Junee Tomelden, and Eckhard Udo Alt. "Safety and Efficacy of Autologous Stem Cell Treatment for Facetogenic Chronic Back Pain." Journal of Personalized Medicine 13, no. 3 (February 28, 2023): 436. http://dx.doi.org/10.3390/jpm13030436.

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Background: Chronic back pain due to facet joint syndrome is a common and debilitating condition. Advances in regenerative medicine have shown that autologous unmodified adipose tissue-derived regenerative cells (ADRC) provide several beneficial effects. These regenerative cells can differentiate into various tissues and exhibit a strong anti-inflammatory potential. ADRCs can be obtained from a small amount of fatty tissue derived from the patient’s abdominal fat. Methods: We report long-term results of 37 patients (age 31–78 years, mean 62.5) suffering from “Facet Joint Syndrome” The pathology was confirmed by clinical, radiological examinations and fluoroscopically guided test injections. Then, liposuction was performed. An amount of 50–100 cc of fat was harvested. To recover stem cells from adipose tissue, we use the CE-certified Transpose RT™ system from InGeneron GmbH. The cells were then injected under fluoroscopic control in the periarticular fat. Follow-up examinations were performed at 1 week, 1 year, and 5 years. Results: Every patient reported improved VAS pain at any follow-up (1 week, 1 year, and 5 years) with ADRCs compared to the baseline. Conclusions: Our observational data indicate that facet joint syndrome patients treated with unmodified adipose tissue-derived regenerative cells experience improved the quality of life in the long term.

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31

Hu, Yu-Chen. "ID:3006 RNA Therapeutics and Anabolic Gene Delivery for Tissue Regeneration." Biomedical Research and Therapy 4, S (September 5, 2017): 18. http://dx.doi.org/10.15419/bmrat.v4is.224.

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Regenerative medicine requires coordinated functions of cells, materials and appropriate signaling. Recent years have witnessed the marriage of regenerative medicine and gene delivery by which various genes encoding anabolic/catabolic proteins or RNA therapeutics are delivered into cells to potentiate the tissue regeneration. This presentation will focus on the use of viral vectors for genetic modification of mesenchymal stem cells derived from bone marrow or adipose tissue for tissue regeneration. In particular, emphasis is placed on the applications of baculovirus, an emerging nonpathogenic gene delivery vector, for the delivery of various anabolic genes and miRNA mimics/sponges to repair tissues

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Costela-Ruiz, Victor J., Lucía Melguizo-Rodríguez, Chiara Bellotti, Rebeca Illescas-Montes, Deborah Stanco, Carla Renata Arciola, and Enrico Lucarelli. "Different Sources of Mesenchymal Stem Cells for Tissue Regeneration: A Guide to Identifying the Most Favorable One in Orthopedics and Dentistry Applications." International Journal of Molecular Sciences 23, no. 11 (June 6, 2022): 6356. http://dx.doi.org/10.3390/ijms23116356.

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The success of regenerative medicine in various clinical applications depends on the appropriate selection of the source of mesenchymal stem cells (MSCs). Indeed, the source conditions, the quality and quantity of MSCs, have an influence on the growth factors, cytokines, extracellular vesicles, and secrete bioactive factors of the regenerative milieu, thus influencing the clinical result. Thus, optimal source selection should harmonize this complex setting and ensure a well-personalized and effective treatment. Mesenchymal stem cells (MSCs) can be obtained from several sources, including bone marrow and adipose tissue, already used in orthopedic regenerative applications. In this sense, for bone, dental, and oral injuries, MSCs could provide an innovative and effective therapy. The present review aims to compare the properties (proliferation, migration, clonogenicity, angiogenic capacity, differentiation potential, and secretome) of MSCs derived from bone marrow, adipose tissue, and dental tissue to enable clinicians to select the best source of MSCs for their clinical application in bone and oral tissue regeneration to delineate new translational perspectives. A review of the literature was conducted using the search engines Web of Science, Pubmed, Scopus, and Google Scholar. An analysis of different publications showed that all sources compared (bone marrow mesenchymal stem cells (BM-MSCs), adipose tissue mesenchymal stem cells (AT-MSCs), and dental tissue mesenchymal stem cells (DT-MSCs) are good options to promote proper migration and angiogenesis, and they turn out to be useful for gingival, dental pulp, bone, and periodontal regeneration. In particular, DT-MSCs have better proliferation rates and AT and G-MSC sources showed higher clonogenicity. MSCs from bone marrow, widely used in orthopedic regenerative medicine, are preferable for their differentiation ability. Considering all the properties among sources, BM-MSCs, AT-MSCs, and DT-MSCs present as potential candidates for oral and dental regeneration.

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Kaewsuwan, Sireewan, Seung Yong Song, Ji Hye Kim, and Jong-Hyuk Sung. "Mimicking the functional niche of adipose-derived stem cells for regenerative medicine." Expert Opinion on Biological Therapy 12, no. 12 (September 6, 2012): 1575–88. http://dx.doi.org/10.1517/14712598.2012.721763.

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Fizzah Arif, Mohammad Fazlur Rahman, and Ceemal Fareed Khan. "Adipose derived stem cells for the peripheral nerve regeneration: review of techniques and clinical implications." Journal of the Pakistan Medical Association 73, no. 2 (January 25, 2023): S148—S154. http://dx.doi.org/10.47391/jpma.akus-24.

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Adipose tissue is considered as a multipotent organ with multiple cellular varieties, like adipose derived stem cells with ability to differentiate into nerve cells. This review is an attempt to summarize the techniques of harvesting, isolating and delivery of adipose derived stem cells to injured nerve area and various interactions involved in the release of neurotrophic and angiogenic factors from stem cells. Neuro-regenerative potential of ADSCs is explained on the basis of “Paracrine hypothesis”, according to which ADSCs secrete multiple neurotrophic factors and upregulates secretion of these neurotrophic factors by Schwann cells, leading to improved myelination, regeneration and decreases nerve fibrosis. ADSCs are easily available in abundance and undergo multi-step processing before grafting to nerve injury site. Acute inflammation, hypoxia and co-culturing with Schwann cells promotes neural differentiation of ADSCs. ADSCs and Schwann cells are reported to have similar mitogenic and differentiation factors, Continued...

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35

Luck, Joshua, Benjamin D. Weil, Mark Lowdell, and Afshin Mosahebi. "Adipose-Derived Stem Cells for Regenerative Wound Healing Applications: Understanding the Clinical and Regulatory Environment." Aesthetic Surgery Journal 40, no. 7 (August 13, 2019): 784–99. http://dx.doi.org/10.1093/asj/sjz214.

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Abstract There is growing interest in the regenerative potential of adipose-derived stem cells (ADSCs) for wound healing applications. ADSCs have been shown to promote revascularization, activate local stem cell niches, reduce oxidative stress, and modulate immune responses. Combined with the fact that they can be harvested in large numbers with minimal donor site morbidity, ADSC products represent promising regenerative cell therapies. This article provides a detailed description of the defining characteristics and therapeutic potential of ADSCs, with a focus on understanding how ADSCs promote tissue regeneration and repair. It summarizes the current regulatory environment governing the use of ADSC products across Europe and the United States and examines how various adipose-derived products conform to the current UK legislative framework. Advice is given to clinicians and researchers on how novel ADSC therapeutics may be developed in accordance with regulatory guidelines.

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36

Berebichez-Fridman, Roberto, and Pablo R. Montero-Olvera. "Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review." Sultan Qaboos University Medical Journal [SQUMJ] 18, no. 3 (December 19, 2018): 264. http://dx.doi.org/10.18295/squmj.2018.18.03.002.

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First discovered by Friedenstein in 1976, mesenchymal stem cells (MSCs) are adult stem cells found throughout the body that share a fixed set of characteristics. Discovered initially in the bone marrow, this cell source is considered the gold standard for clinical research, although various other sources—including adipose tissue, dental pulp, mobilised peripheral blood and birth-derived tissues—have since been identified. Although similar, MSCs derived from different sources possess distinct characteristics, advantages and disadvantages, including their differentiation potential and proliferation capacity, which influence their applicability. Hence, they may be used for specific clinical applications in the fields of regenerative medicine and tissue engineering. This review article summarises current knowledge regarding the various sources, characteristics and therapeutic applications of MSCs.Keywords: Mesenchymal Stem Cells; Adult Stem Cells; Regenerative Medicine; Cell Differentiation; Tissue Engineering.

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37

Smok, Carolina, Manuel Meruane, and Mariana Rojas. "Implantation of Autologous Stem Cells Derived from Adipose Tissue in Rat Bone Fractures." International Journal of Medical and Surgical Sciences 1, no. 2 (October 26, 2018): 105–15. http://dx.doi.org/10.32457/ijmss.2014.013.

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Stem cells derived from adipose tissue (ASCs) correspond to a major advance with respect to the bone regenerative medicine, as they have the ability for self-renewal, differentiation and paracrine stimulation to various types of tissues including bone and cartilage. The hypothesis of this study considers that fractures treated with ASCs, time decreases bone regeneration and vascularization increases, aiming to histologically evaluate bone regeneration and vascularization in these fractures. To accomplish this, 24 young male Sprague Dawley rats were used. The specimens were divided into two groups: Group A (treated) and group B (control). In both groups, the rats were euthanized at 11 and 21 days post-fracture. Statistically significant difference was observed in the number of newly formed trabeculae and vascular density in the treated group compared to control group concluded that rats treated with ASCs have a higher rate and better angiogenic bone regeneration, especially given the ability to synthesize components of the extracellular matrix of these cell, and the production of angiogenic growth factors.

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38

Fortier, Lisa Ann, Laurie Ruth Goodrich, Iris Ribitsch, Lauren Virginia Schnabel, David Owen Shepard, Ashlee Elizabeth Watts, and Roger Kenneth Whealands Smith. "One health in regenerative medicine: report on the second Havemeyer symposium on regenerative medicine in horses." Regenerative Medicine 15, no. 6 (June 2020): 1775–87. http://dx.doi.org/10.2217/rme-2019-0143.

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Regenerative medicine is commonly used in human and equine athletes. Potential therapies include culture expanded stem cells, stromal vascular fraction of adipose tissue, platelet-rich plasma, bone marrow concentrate, or autologous conditioned serum. The purpose of this manuscript is to disseminate findings from a workshop on the development of translational regenerative medicine in the equine field. Five themes emerged: stem cell characterization and tenogenic differentiation; interactions between mesenchymal stem cells, other cells and the environment; scaffolds and cell packaging; blood- and bone marrow-based regenerative medicines; clinical use of regenerative therapies. Evidence gained through the use of regenerative medicine applications in the horse should continue to translate to the human patient, bringing novel regenerative therapies to both humans and horses.

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Pak, Jaewoo, Jung Hun Lee, and Sang Hee Lee. "Regenerative Repair of Damaged Meniscus with Autologous Adipose Tissue-Derived Stem Cells." BioMed Research International 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/436029.

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Mesenchymal stem cells (MSCs) are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee.

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Marra, Kacey G., and J. Peter Rubin. "Book Review: Adipose Stem Cells and Regenerative Medicine." Aesthetic Surgery Journal 33, no. 8 (November 2013): NP1—NP2. http://dx.doi.org/10.1177/1090820x13511266.

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Kuroda, Shinji. "Attempt to regenerate tooth extraction cavity by three dimensional culture construct using buccal adipose-derived stem cells." Impact 2019, no. 8 (November 26, 2019): 12–14. http://dx.doi.org/10.21820/23987073.2019.8.12.

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Bones are the scaffolding of our bodies, without which we have no structure or anchoring points for muscles, tendons and teeth. As strong as they are though, bones often break or suffer from diseases like cancer, osteoporosis or genetic disorders which impede their proper development. While a broken bone can heal and partially regenerate, in the cases of severe bone defects or injuries doctors have long relied on artificial replacements and various other artificial fixes due to the limitations in bone regeneration. Everything from joint replacements to dental implants has relied on synthetic materials anchored to existing bone. This approach is useful and helps many people but has its limitations. Regenerative dental expert Dr Shinji Kuroda, Junior Associate Professor in the Department of Oral Implantology and Regenerative Dental Medicine at the Tokyo Medical and Dental University, explains that in some cases, infection issues arise from placing foreign objects in the body, and in the case of dental implants there is often not enough bone to anchor implants to. For example, following a tooth extraction the bone, within which the tooth sockets sit, the alveolar ridge, experiences a reduction. 'This reduction is a physiological process and results in reduced stability and aesthetic quality of the dental implants used to replace the extracted tooth,' observes Kuroda. 'Despite numerous strategies to prevent this physiological change, such as immediate implant placement into the fresh extraction site, definitive treatment strategies have not yet been discovered to mitigate this bone loss.' In situations like this or in the case of congenital defects that lead to severe bone damage or loss, the best way forward lies in the promise of regenerative medicine techniques to regrow bone.

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Georgiev-Hristov, Tihomir, Mariano García-Arranz, Jacobo Trébol-López, Paula Barba-Recreo, and Damián García-Olmo. "Searching for the Optimal Donor for Allogenic Adipose-Derived Stem Cells: A Comprehensive Review." Pharmaceutics 14, no. 11 (October 29, 2022): 2338. http://dx.doi.org/10.3390/pharmaceutics14112338.

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Adipose-derived stem cells comprise several clinically beneficial qualities that have been explored in basic research and have motivated several clinical studies with promising results. After being approved in the European Union, UK, Switzerland, Israel, and Japan, allogeneic adipose-derived stem cells (darvadstrocel) have been recently granted a regenerative medicine advanced therapy (RMAT) designation by US FDA for complex perianal fistulas in adults with Crohn’s disease. This huge scientific step is likely to impact the future spread of the indications of allogeneic adipose-derived stem cell applications. The current knowledge on adipose stem cell harvest describes quantitative and qualitative differences that could be influenced by different donor conditions and donor sites. In this comprehensive review, we summarize the current knowledge on the topic and propose donor profiles that could provide the optimal initial quality of this living drug, as a starting point for further applications and studies in different pathological conditions.

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Shimozono, Yoshiharu, Lisa Fortier, Donald Brown, and John Kennedy. "Adipose-Based Therapies for Knee Pain—Fat or Fiction." Journal of Knee Surgery 32, no. 01 (November 30, 2018): 055–64. http://dx.doi.org/10.1055/s-0038-1672155.

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AbstractRegenerative cell therapies are emerging as promising treatments for numerous musculoskeletal conditions, including knee osteoarthritis (OA). Adipose-derived stem cells and possibly other adipose-based therapies have a greater chondrogenic potential than stem cells derived from bone marrow, and thus a lot of attention is being placed on them as potential regenerative agents in the treatment of knee OA. Several types of adipose-based therapies have good basic science and preclinical data supporting their translation to human therapeutic intervention. Cultured, adipose-derived stem cells appear to be good source of bioactive cells with convenient accessibility, relative abundance, and well-documented regenerative capacity. Non-culture expanded adipose-based therapy, in the forms of stromal vascular fraction and most recently micronized adipose tissue (MAT), have been utilized in patients to treat OA and other cartilage abnormalities with encouraging preliminary data. These adipose-based therapies have shown a lot of therapeutic potential; however, because of the regulatory restrictions on enzymatic isolation and cell expansion, only MAT is currently available in clinical practice in the United States. While no serious adverse reactions have been reported, adipose-derived therapies also have the potential for adverse reactions including inflammation and infection. The current review provides an update on the latest research and presents this evidence on the therapeutic potential of adipose-based therapies in the treatment of knee OA.

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Alonso-Goulart, Vivian, Loyna Nobile Carvalho, Ana Leticia Galante Marinho, Bianca Lourenço de Oliveira Souza, Gabriela de Aquino Pinto Palis, Henrique Guerra Drumond Lage, Isabela Lemos de Lima, et al. "Biomaterials and Adipose-Derived Mesenchymal Stem Cells for Regenerative Medicine: A Systematic Review." Materials 14, no. 16 (August 18, 2021): 4641. http://dx.doi.org/10.3390/ma14164641.

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The use of biological templates for the suitable growth of adipose-derived mesenchymal stem cells (AD-MSC) and “neo-tissue” construction has exponentially increased over the last years. The bioengineered scaffolds still have a prominent and biocompatible framework playing a role in tissue regeneration. In order to supply AD-MSCs, biomaterials, as the stem cell niche, are more often supplemented by or stimulate molecular signals that allow differentiation events into several strains, besides their secretion of cytokines and effects of immunomodulation. This systematic review aims to highlight the details of the integration of several types of biomaterials used in association with AD-MSCs, collecting notorious and basic data of in vitro and in vivo assays, taking into account the relevance of the interference of the cell lineage origin and handling cell line protocols for both the replacement and repairing of damaged tissues or organs in clinical application. Our group analyzed the quality and results of the 98 articles selected from PubMed, Scopus and Web of Science. A total of 97% of the articles retrieved demonstrated the potential in clinical applications. The synthetic polymers were the most used biomaterials associated with AD-MSCs and almost half of the selected articles were applied on bone regeneration.

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45

Peng, Chunyang, Li Lu, Yajiao Li, and Jingqiong Hu. "Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells." Cell Transplantation 28, no. 1_suppl (December 2019): 66S—75S. http://dx.doi.org/10.1177/0963689719888619.

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Human adipose-derived stem cells are used in regenerative medicine for treating various diseases including osteoarthritis, degenerative arthritis, cartilage or tendon injury, etc. However, their use in neurological disorders is limited, probably due to the lack of a quick and efficient induction method of transforming these cells into neural stem or progenitor cells. In this study, we reported a highly efficient and simple method to induce adipose-derived stem cells into neural progenitor cells within 12 hours, using serum-free culture combined with a well-defined induction medium (epidermal growth factor 20 ng/ml and basic fibroblast growth factor, both at 20 ng/ml, with N2 and B27 supplements). These adipose-derived stem cell-derived neural progenitor cells grow as neurospheres, can self-renew to form secondary neurospheres, and can be induced to become neurons and glial cells. Real-time polymerase chain reaction showed significantly upregulated expression of neurogenic genes Sox2 and Nestin with a moderate increase in stemness gene expression. Raybio human growth factor analysis showed a significantly upregulated expression of multiple neurogenic and angiogenic cytokines such as brain-derived neurotrophic factor, glial cell line-derived neurotrophic growth factor, nerve growth factor, basic fibroblast growth factor and vascular endothelial growth factor etc. Therefore, adipose-derived stem cell-derived neurospheres can be a new source of neural progenitor cells and hold great potential for future cell replacement therapy for treatment of various refractory neurological diseases.

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Ong, Wee Kiat, Smarajit Chakraborty, and Shigeki Sugii. "Adipose Tissue: Understanding the Heterogeneity of Stem Cells for Regenerative Medicine." Biomolecules 11, no. 7 (June 22, 2021): 918. http://dx.doi.org/10.3390/biom11070918.

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Adipose-derived stem cells (ASCs) have been increasingly used as a versatile source of mesenchymal stem cells (MSCs) for diverse clinical investigations. However, their applications often become complicated due to heterogeneity arising from various factors. Cellular heterogeneity can occur due to: (i) nomenclature and criteria for definition; (ii) adipose tissue depots (e.g., subcutaneous fat, visceral fat) from which ASCs are isolated; (iii) donor and inter-subject variation (age, body mass index, gender, and disease state); (iv) species difference; and (v) study design (in vivo versus in vitro) and tools used (e.g., antibody isolation and culture conditions). There are also actual differences in resident cell types that exhibit ASC/MSC characteristics. Multilineage-differentiating stress-enduring (Muse) cells and dedifferentiated fat (DFAT) cells have been reported as an alternative or derivative source of ASCs for application in regenerative medicine. In this review, we discuss these factors that contribute to the heterogeneity of human ASCs in detail, and what should be taken into consideration for overcoming challenges associated with such heterogeneity in the clinical use of ASCs. Attempts to understand, define, and standardize cellular heterogeneity are important in supporting therapeutic strategies and regulatory considerations for the use of ASCs.

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47

Si, Zizhen, Xue Wang, Changhui Sun, Yuchun Kang, Jiakun Xu, Xidi Wang, and Yang Hui. "Adipose-derived stem cells: Sources, potency, and implications for regenerative therapies." Biomedicine & Pharmacotherapy 114 (June 2019): 108765. http://dx.doi.org/10.1016/j.biopha.2019.108765.

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Ogawa, Rei, and Shuichi Mizuno. "Cartilage Regeneration Using Adipose-Derived Stem Cells." Current Stem Cell Research & Therapy 5, no. 2 (June 1, 2010): 129–32. http://dx.doi.org/10.2174/157488810791268627.

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49

Zhong, Yu-chen, Shi-chun Wang, Yin-he Han, and Yu Wen. "Recent Advance in Source, Property, Differentiation, and Applications of Infrapatellar Fat Pad Adipose-Derived Stem Cells." Stem Cells International 2020 (March 7, 2020): 1–14. http://dx.doi.org/10.1155/2020/2560174.

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Infrapatellar fat pad (IPFP) can be easily obtained during knee surgery, which avoids the damage to patients for obtaining IPFP. Infrapatellar fat pad adipose-derived stem cells (IPFP-ASCs) are also called infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) because the morphology of IPFP-ASCs is similar to that of bone marrow mesenchymal stem cells (BM-MSCs). IPFP-ASCs are attracting more and more attention due to their characteristics suitable to regenerative medicine such as strong proliferation and differentiation, anti-inflammation, antiaging, secreting cytokines, multipotential capacity, and 3D culture. IPFP-ASCs can repair articular cartilage and relieve the pain caused by osteoarthritis, so most of IPFP-related review articles focus on osteoarthritis. This article reviews the anatomy and function of IPFP, as well as the discovery, amplification, multipotential capacity, and application of IPFP-ASCs in order to explain why IPFP-ASC is a superior stem cell source in regenerative medicine.

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Kanno, Hiroshi, Shutaro Matsumoto, Tetsuya Yoshizumi, Kimihiro Nakahara, Masamichi Shinonaga, Atsuhiko Kubo, Satoshi Fujii, et al. "SOCS7-Derived BC-Box Motif Peptide Mediated Cholinergic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells." International Journal of Molecular Sciences 24, no. 3 (February 1, 2023): 2786. http://dx.doi.org/10.3390/ijms24032786.

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Adipose-derived mesenchymal stem cells (ADMSCs) are a type of pluripotent somatic stem cells that differentiate into various cell types such as osteoblast, chondrocyte, and neuronal cells. ADMSCs as donor cells are used to produce regenerative medicines at hospitals and clinics. However, it has not been reported that ADMSCs were differentiated to a specific type of neuron with a peptide. Here, we report that ADMSCs differentiate to the cholinergic phenotype of neurons by the SOCS7-derived BC-box motif peptide. At operations for patients with neurological disorders, a small amount of subcutaneous fat was obtained. Two weeks later, adipose-derived mesenchymal stem cells (ADMSCs) were isolated and cultured for a further 1 to 2 weeks. Flow cytometry analysis for characterization of ADMSCs was performed with CD73, CD90, and CD105 as positive markers, and CD14, CD31, and CD56 as negative markers. The results showed that cultured cells were compatible with ADMSCs. Immunocytochemical studies showed naïve ADMSCs immunopositive for p75NTR, RET, nestin, keratin, neurofilament-M, and smooth muscle actin. ADMSCs were suggested to be pluripotent stem cells. A peptide corresponding to the amino-acid sequence of BC-box motif derived from SOCS7 protein was added to the medium at a concentration of 2 μM. Three days later, immunocytochemistry analysis, Western blot analysis, ubiquitination assay, and electrophysiological analysis with patch cramp were performed. Immunostaining revealed the expression of neurofilament H (NFH), choline acetyltransferase (ChAT), and tyrosine hydroxylase (TH). In addition, Western blot analysis showed an increase in the expression of NFH, ChAT, and TH, and the expression of ChAT was more distinct than TH. Immunoprecipitation with JAK2 showed an increase in the expression of ubiquitin. Electrophysiological analysis showed a large holding potential at the recorded cells through path electrodes. The BC-box motif peptide derived from SOCS7 promoted the cholinergic differentiation of ADMSCs. This novel method will contribute to research as well as regenerative medicine for cholinergic neuron diseases.

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