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Journal articles on the topic 'Nucleus Pulposus Regeneration'

Author: Grafiati

Published: 6 September 2023

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1

Kregar Velikonja, Nevenka, Jill Urban, Mirjam Fröhlich, Cornelia Neidlinger-Wilke, Dimitris Kletsas, Urska Potocar, Sarah Turner, and Sally Roberts. "Cell sources for nucleus pulposus regeneration." European Spine Journal 23, S3 (December 3, 2013): 364–74. http://dx.doi.org/10.1007/s00586-013-3106-9.

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2

Yu, Lei, Zi-Jie Sun, Quan-Chang Tan, Shuang Wang, Wei-Heng Wang, Xiang-Qun Yang, and Xiao-Jian Ye. "Thermosensitive injectable decellularized nucleus pulposus hydrogel as an ideal biomaterial for nucleus pulposus regeneration." Journal of Biomaterials Applications 35, no. 2 (April 26, 2020): 182–92. http://dx.doi.org/10.1177/0885328220921328.

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Extracellular matrix loss is one of the early manifestations of intervertebral disc degeneration. Stem cell-based tissue engineering creates an appropriate microenvironment for long term cell survival, promising for NP regeneration. We created a decellularized nucleus pulposus hydrogel (DNPH) from fresh bovine nucleus pulposus. Decellularization removed NP cells effectively, while highly preserving their structures and major biochemical components, such as glycosaminoglycan and collagen II. DNPH could be gelled as a uniform grid structure in situ at 37°C for 30 min. Adding adipose marrow-derived mesenchymal stem cells into the hydrogel for three-dimensional culture resulted in good bioactivity and biocompatibility in vitro. Meanwhile, NP-related gene expression significantly increased without the addition of exogenous biological factors. In summary, the thermosensitive and injectable hydrogel, which has low toxicity and inducible differentiation, could serve as a bio-scaffold, bio-carrier, and three-dimensional culture system. Therefore, DNPH has an outstanding potential for intervertebral disc regeneration.

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3

Patt, Stephan, Mario Brock, Heinz Michael Mayer, Carl Schreiner, and Lamartine Pedretti. "Nucleus Pulposus Regeneration After Chemonucleolysis with chymopapain?" Spine 18, no. 2 (February 1993): 227–31. http://dx.doi.org/10.1097/00007632-199302000-00009.

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4

Risbud, Makarand V., Irving M. Shapiro, Alexander R. Vaccaro, and Todd J. Albert. "Stem cell regeneration of the nucleus pulposus." Spine Journal 4, no. 6 (November 2004): S348—S353. http://dx.doi.org/10.1016/j.spinee.2004.07.031.

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5

Krouwels, Anita, Juvita D. Iljas, Angela H. M. Kragten, Wouter J. A. Dhert, F. Cumhur Öner, Marianna A. Tryfonidou, and Laura B. Creemers. "Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration." International Journal of Molecular Sciences 21, no. 8 (April 14, 2020): 2720. http://dx.doi.org/10.3390/ijms21082720.

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Matrix production by nucleus pulposus (NP) cells, the cells residing in the center of the intervertebral disc, can be stimulated by growth factors. Bone morphogenetic proteins (BMPs) hold great promise. Although BMP2 and BMP7 have been used most frequently, other BMPs have also shown potential for NP regeneration. Heterodimers may be more potent than single homodimers, but it is not known whether combinations of homodimers would perform equally well. In this study, we compared BMP2, BMP4, BMP6, and BMP7, their combinations and heterodimers, for regeneration by human NP cells. The BMPs investigated induced variable matrix deposition by NP cells. BMP4 was the most potent, both in the final neotissue glysosaminoglycan content and incorporation efficiency. Heterodimers BMP2/6H and BMP2/7H were more potent than their respective homodimer combinations, but not the BMP4/7H heterodimer. The current results indicate that BMP4 might have a high potential for regeneration of the intervertebral disc. Moreover, the added value of BMP heterodimers over their respective homodimer BMP combinations depends on the BMP combination applied.

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6

Bodnarchuk, J. A., M. V. Khyzhnjak, О. О. Potapov, and N. G. Chopik. "BIOCHEMICAL AND BIOMECHANICAL SUBSTANTIATION OF REPARATIVE REGENERATION OF INTERVERTEBRAL DISCS IN PATIENTS WITH DEGENERATIVE DISC DISEASES." Eastern Ukrainian Medical Journal 8, no. 3 (2020): 249–54. http://dx.doi.org/10.21272/eumj.2020;8(3):249-254.

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Degenerative disc diseases occupy the second place in the overall structure of morbidity with temporary disability. In 40% of patients with spinal osteochondrosis, diseases of the locomotor apparatus and connective tissue cause primary disability. Disc degeneration is a pathological process that is the main cause of low back pain and is observed in the vast majority of people at some point in their lives. The influence of mechanical stress leads to degenerative changes in the tissues of the nucleus pulposus of the intervertebral disc. Limited transport and low cellular saturation of the discs hinder recovery, make the intervertebral disc particularly vulnerable to injury, and contribute to the appearance of morphological tissue damage associated with the processes of biological aging. The pathological process involves all structural elements of the intervertebral disc. The earliest manifestations of disc degeneration usually occur in the nucleus pulposus, where a reduced content of proteoglycans disrupts mechanical function, which leads to progressive morphological degeneration of the entire intervertebral segment. Existing treatment methods (both surgical and conservative) are not able to adjust the number of cells in the nucleus pulposus and are unable to stop the pathological process in the intervertebral disc. Prevention of degeneration or repair of the intervertebral disc is a potential treatment for lumbar pain syndromes. Cell therapy has become a subject of great interest, as new research reports significant regenerative potential for many cellular sources, including the regeneration of the nucleus pulposus region of the intervertebral disc. The use and implementation of modern cell therapy in practical neurosurgery allows us to approach the problem of intervertebral disc degeneration at a new qualitative level with the use of multipotent cells, biochemical peptides in the reparative processes of the nucleus pulposus, as a possibility of treatment and prevention of vertebrogenic pain syndromes in the future. Keywords intervertebral disc, nucleus pulposus, cell therapy, transplantation, degenerative changes, reparation

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7

Peng, Xuan, Lingjia Yu, Lin Shi, Huajun Dong, Xiaohui Meng, and Bin Zhu. "Polymeric hydrogels and decellularized nucleus pulposus extracellular matrix technology for nucleus pulposus repair and regeneration." Polymer Testing 117 (January 2023): 107854. http://dx.doi.org/10.1016/j.polymertesting.2022.107854.

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8

Zhu, Yanxia, Jie Tan, Hongxia Zhu, Guangyao Lin, Fei Yin, Liang Wang, Kedong Song, Yiwei Wang, Guangqian Zhou, and Weihong Yi. "Development of kartogenin-conjugated chitosan–hyaluronic acid hydrogel for nucleus pulposus regeneration." Biomaterials Science 5, no. 4 (2017): 784–91. http://dx.doi.org/10.1039/c7bm00001d.

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9

Hodgkinson, Tom, Francis Wignall, Judith A. Hoyland, and Stephen M. Richardson. "High BMPR2 expression leads to enhanced SMAD1/5/8 signalling and GDF6 responsiveness in human adipose-derived stem cells: implications for stem cell therapies for intervertebral disc degeneration." Journal of Tissue Engineering 11 (January 2020): 204173142091933. http://dx.doi.org/10.1177/2041731420919334.

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Stem cell–based regenerative strategies are promising for intervertebral disc degeneration. Stimulation of bone-marrow- and adipose-derived multipotent stem cells with recombinant human growth differentiation factor 6 (rhGDF6) promotes anabolic nucleus pulposus like phenotypes. In comparison to mesenchymal stem cells, adipose-derived multipotent stem cells exhibit greater NP-marker gene expression and proteoglycan-rich matrix production. To understand these response differences, we investigated bone morphogenetic protein receptor profiles in donor-matched human mesenchymal stem cells and adipose-derived multipotent stem cells, determined differences in rhGDF6 signalling and their importance in NP-like differentiation between cell populations. Bone morphogenetic protein receptor expression in mesenchymal stem cells and adipose-derived multipotent stem cells revealed elevated and less variable expression of BMPR2 in adipose-derived multipotent stem cells, which corresponded with increased downstream pathway activation (SMAD1/5/8, ERK1/2). Inhibitor studies demonstrated SMAD1/5/8 signalling was required for rhGDF6-induced nucleus-pulposus-like adipose-derived multipotent stem cell differentiation, while ERK1/2 contributed significantly to critical nucleus pulposus gene expression, aggrecan and type II collagen production. These data inform cell regenerative therapeutic choices for intervertebral disc degeneration regeneration and identify further potential optimisation targets.

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10

Li, Zhen, Keren Mevorat Kaplan, Abraham Wertzel, Marianna Peroglio, Boaz Amit, Mauro Alini, Sibylle Grad, and Avner Yayon. "Biomimetic fibrin–hyaluronan hydrogels for nucleus pulposus regeneration." Regenerative Medicine 9, no. 3 (May 2014): 309–26. http://dx.doi.org/10.2217/rme.14.5.

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11

Priyadarshani, P., Y. Li, and L. Yao. "Advances in biological therapy for nucleus pulposus regeneration." Osteoarthritis and Cartilage 24, no. 2 (February 2016): 206–12. http://dx.doi.org/10.1016/j.joca.2015.08.014.

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12

Francisco, Aubrey T., Robert J. Mancino, Robby D. Bowles, Jonathan M. Brunger, David M. Tainter, Yi-Te Chen, William J. Richardson, Farshid Guilak, and Lori A. Setton. "Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration." Biomaterials 34, no. 30 (October 2013): 7381–88. http://dx.doi.org/10.1016/j.biomaterials.2013.06.038.

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13

Simonetti, L., and C. Barbara. "Reflections on the Nucleus Pulposus." Rivista di Neuroradiologia 11, no. 3 (June 1998): 399–402. http://dx.doi.org/10.1177/197140099801100325.

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The intervertebral disc is usually divided into two parts, the anulus fibrosus and the nucleus pulposus. However, they are not considered two separate anatomic parts since one is essentially part of the other and this should be borne in mind to understand the process of ageing. The intervertebral disc should therefore be thought of as a dynamically evolving anatomo-functional unit. The dynamics of this process were investigated by studying the histobiochemistry of the acellular matrix of the joint cartilage in general and that of the intervertebral disc in particular to understand the effects of this arrangement on the stuctural changes to the disc induced by biomechanical stress, especially during ageing. Lastly, we focussed on the disc's nutritional mechanisms in order to examine “disc degeneration” as a sign of metabolic impairment of the nucleus pulposus and “disc regeneration”. This concept was unknown until recently and is currently monitored in percutaneous controls following treatment for disc disease.

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14

Lang, Gernot, Zhen Li, Xu Chen, Hagit Sacks, Avner Yayon, Franz Weber, Mauro Alini, and Sibylle Grad. "BMP 2/7 Release System for Nucleus Pulposus Regeneration." Global Spine Journal 6, no. 1_suppl (April 2016): s—0036–1582593—s—0036–1582593. http://dx.doi.org/10.1055/s-0036-1582593.

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15

Halloran, Damien O., Sibylle Grad, Martin Stoddart, Peter Dockery, Mauro Alini, and Abhay S. Pandit. "An injectable cross-linked scaffold for nucleus pulposus regeneration." Biomaterials 29, no. 4 (February 2008): 438–47. http://dx.doi.org/10.1016/j.biomaterials.2007.10.009.

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16

Meisel, Hans-Jörg, Tim Ganey, William Hutton, Tim Moseley, and Marc Hedrick. "115. Nucleus Pulposus Regeneration Using Fresh Autologous Adipose-derived Cells." Spine Journal 7, no. 5 (September 2007): 56S. http://dx.doi.org/10.1016/j.spinee.2007.07.137.

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17

Meisel, H. J., T. Ganey, W. Hutton, T. Moseley, and M. Hedrick. "19.4 Nucleus pulposus regeneration using fresh autologous adipose- derived cells." Osteoarthritis and Cartilage 15 (2007): B76. http://dx.doi.org/10.1016/s1063-4584(07)61312-0.

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18

Zhou, Xiaopeng, Jingkai Wang, Xianpeng Huang, Weijing Fang, Yiqing Tao, Tengfei Zhao, Chengzhen Liang, Jianming Hua, Qixin Chen, and Fangcai Li. "Injectable decellularized nucleus pulposus-based cell delivery system for differentiation of adipose-derived stem cells and nucleus pulposus regeneration." Acta Biomaterialia 81 (November 2018): 115–28. http://dx.doi.org/10.1016/j.actbio.2018.09.044.

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19

Harmon, Matthew D., Daisy M. Ramos, D. Nithyadevi, Rosalie Bordett, Swetha Rudraiah, Syam P. Nukavarapu, Isaac L. Moss, and Sangamesh G. Kumbar. "Growing a backbone – functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions." Biomaterials Science 8, no. 5 (2020): 1216–39. http://dx.doi.org/10.1039/c9bm01288e.

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20

Mu, Jiang, Zhize Liu, Shuang Chen, Haoming Niu, Guiqi Zhang, and Xiaodong Lian. "Intervertebral Disk Regeneration in a Rat Model via a Nanocomposite Collagen Hydrogel Loaded with Galanthus Extract: An In Vitro and In Vivo Study." Journal of Biomedical Nanotechnology 18, no. 12 (December 1, 2022): 2804–8. http://dx.doi.org/10.1166/jbn.2022.3483.

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In the current study, Galanthus extract was loaded into electrospun gelatin scaffolds using an electrospun method and then crushed. The resulting nanofibers were loaded into a collagen hydrogel to develop a filler material to treat nucleus pulposus injuries in the intervertebral disks. The nanocomposite hydrogel was studied regarding its biocompatibility, antiinflammatory activity, and swelling behavior. In Vivo study was performed in a rat model of intervertebral disk injury. Histopathological studies showed that the animals treated with the nanocomposite hydrogel restored its nucleus pulposus to a significantly higher extent than other experimental groups.

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21

Ishii, Takayuki, Daisuke Sakai, Jordy Schol, Tomoko Nakai, Kaori Suyama, and Masahiko Watanabe. "Sciatic nerve regeneration by transplantation ofin vitrodifferentiated nucleus pulposus progenitor cells." Regenerative Medicine 12, no. 4 (April 2017): 365–76. http://dx.doi.org/10.2217/rme-2016-0168.

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22

Park, Sang-Hyug, Hongsik Cho, Eun Seok Gil, Biman B. Mandal, Byoung-Hyun Min, and David L. Kaplan. "Silk-Fibrin/Hyaluronic Acid Composite Gels for Nucleus Pulposus Tissue Regeneration." Tissue Engineering Part A 17, no. 23-24 (December 2011): 2999–3009. http://dx.doi.org/10.1089/ten.tea.2010.0747.

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23

Alinejad, Yasaman, Atma Adoungotchodo, Michael P. Grant, Laura M. Epure, John Antoniou, Fackson Mwale, and Sophie Lerouge. "Injectable Chitosan Hydrogels with Enhanced Mechanical Properties for Nucleus Pulposus Regeneration." Tissue Engineering Part A 25, no. 5-6 (March 2019): 303–13. http://dx.doi.org/10.1089/ten.tea.2018.0170.

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24

Tao, Yi-Qing, Cheng-Zhen Liang, Hao Li, Yu-Jie Zhang, Fang-Cai Li, Gang Chen, and Qi-Xin Chen. "Potential of co-culture of nucleus pulposus mesenchymal stem cells and nucleus pulposus cells in hyperosmotic microenvironment for intervertebral disc regeneration." Cell Biology International 37, no. 8 (April 18, 2013): 826–34. http://dx.doi.org/10.1002/cbin.10110.

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25

Suryandaru, H. V., A. I. Aziz, N. Hanifah, and A. Rasyida. "Alginate/PVA/chitosan injection composites as scaffold material for nucleus pulposus regeneration." IOP Conference Series: Earth and Environmental Science 649, no. 1 (February 1, 2021): 012019. http://dx.doi.org/10.1088/1755-1315/649/1/012019.

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26

R. Jackson, Alicia. "Notochordal Nucleus Pulposus Cells: Prospective Strategies for Intervertebral Disc Repair and Regeneration." Current Tissue Engineering 4, no. 2 (October 27, 2015): 77–85. http://dx.doi.org/10.2174/2211542004666150713185006.

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27

Perez-Cruet, Mick J., Rasul Chaudhry, Lee O. Chieng, Christina McKee, and Aaron Rapp. "173 Hydrogel Matrix Human Stem Cell Based Nucleus Pulposus Intervertebral Disc Regeneration." Neurosurgery 68, Supplement_1 (March 1, 2022): 52. http://dx.doi.org/10.1227/neu.0000000000001880_173.

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28

Krouwels, A., L. Iljas, S. Plomp, W. Dhert, C. Oner, and L. Creemers. "BMPs Enhance in Vitro Tissue Regeneration by Human Degenerated Nucleus Pulposus Cells." Global Spine Journal 4, no. 1_suppl (May 2014): s—0034–1376562—s—0034–1376562. http://dx.doi.org/10.1055/s-0034-1376562.

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29

Krouwels, Anita, Ferry P. W. Melchels, Mattie H. P. van Rijen, F. Cumhur Öner, Wouter J. A. Dhert, Marianna A. Tryfonidou, and Laura B. Creemers. "Comparing Hydrogels for Human Nucleus Pulposus Regeneration: Role of Osmolarity During Expansion." Tissue Engineering Part C: Methods 24, no. 4 (April 2018): 222–32. http://dx.doi.org/10.1089/ten.tec.2017.0226.

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30

Su, Wen-Yu, Yu-Chun Chen, and Feng-Huei Lin. "Injectable oxidized hyaluronic acid/adipic acid dihydrazide hydrogel for nucleus pulposus regeneration." Acta Biomaterialia 6, no. 8 (August 2010): 3044–55. http://dx.doi.org/10.1016/j.actbio.2010.02.037.

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31

Xu, Yichang, Yong Gu, Feng Cai, Kun Xi, Tianwen Xin, Jincheng Tang, Liang Wu, et al. "Metabolism Balance Regulation via Antagonist‐Functionalized Injectable Microsphere for Nucleus Pulposus Regeneration." Advanced Functional Materials 30, no. 52 (September 28, 2020): 2006333. http://dx.doi.org/10.1002/adfm.202006333.

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32

Lewis, Gladius. "Nucleus pulposus replacement and regeneration/repair technologies: Present status and future prospects." Journal of Biomedical Materials Research Part B: Applied Biomaterials 100B, no. 6 (May 7, 2012): 1702–20. http://dx.doi.org/10.1002/jbm.b.32712.

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33

Illien-Jünger, Svenja, Dillon D. Sedaghatpour, Damien M. Laudier, Andrew C. Hecht, Sheeraz A. Qureshi, and James C. Iatridis. "Development of a bovine decellularized extracellular matrix-biomaterial for nucleus pulposus regeneration." Journal of Orthopaedic Research 34, no. 5 (December 1, 2015): 876–88. http://dx.doi.org/10.1002/jor.23088.

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34

Xia, Kaishun, Zhe Gong, Jian Zhu, Wei Yu, Yitian Wang, Junjie Wang, Ankai Xu, et al. "Differentiation of Pluripotent Stem Cells into Nucleus Pulposus Progenitor Cells for Intervertebral Disc Regeneration." Current Stem Cell Research & Therapy 14, no. 1 (January 14, 2019): 57–64. http://dx.doi.org/10.2174/1574888x13666180918095121.

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Low back pain (LBP) is one of the world’s most common musculoskeletal diseases and is frequently associated with intervertebral disc degeneration (IDD). While the main cause of IDD is commonly attributed to a reduced number of nucleus pulposus (NP) cells, current treatment strategies (both surgical and more conservative) fail to replenish NP cells or reverse the pathology. Cell replacement therapies are an attractive alternative for treating IDD. However, injecting intervertebral disc (IVD) cells, chondrocytes, or mesenchymal stem cells into various animal models of IDD indicate that transplanted cells generally fail to survive and engraft into the avascular IVD niche. Whereas pluripotent stem cells (PSCs), including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), hold great potential for revolutionizing regenerative medicine, current protocols for differentiating these cells into NP-like cells are inadequate. Nucleus pulposus progenitor cells (NPPCs), which are derived from the embryonic notochord, can not only survive within the harsh hypoxic environment of the IVD, but they also efficiently differentiate into NP-like cells. Here we provide an overview of the latest progress in repairing degenerated IVDs using PSCs and NPPCs. We also discuss the molecular pathways by which PSCs differentiate into NPPCs in vitro and in vivo and propose a new, in vivo IDD therapy.

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35

Hegewald, Aldemar A., Michaela Endres, Alexander Abbushi, Mario Cabraja, Christian Woiciechowsky, Kirsten Schmieder, Christian Kaps, and Claudius Thomé. "Adequacy of herniated disc tissue as a cell source for nucleus pulposus regeneration." Journal of Neurosurgery: Spine 14, no. 2 (February 2011): 273–80. http://dx.doi.org/10.3171/2010.10.spine10223.

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Object The object of this study was to characterize the regenerative potential of cells isolated from herniated disc tissue obtained during microdiscectomy. The acquired data could help to evaluate the feasibility of these cells for autologous disc cell transplantation. Methods From each of 5 patients (mean age 45 years), tissue from the nucleus pulposus compartment as well as from herniated disc was obtained separately during microdiscectomy of symptomatic herniated lumbar discs. Cells were isolated, and in vitro cell expansion for cells from herniated disc tissue was accomplished using human serum and fibroblast growth factor-2. For 3D culture, expanded cells were loaded in a fibrin-hyaluronan solution on polyglycolic acid scaffolds for 2 weeks. The formation of disc tissue was documented by histological staining of the extracellular matrix as well as by gene expression analysis of typical disc marker genes. Results Cells isolated from herniated disc tissue showed significant signs of dedifferentiation and degeneration in comparison with cells from tissue of the nucleus compartment. With in vitro cell expansion, further dedifferentiation with distinct suppression of major matrix molecules, such as aggrecan and Type II collagen, was observed. Unlike in previous reports of cells from the nucleus compartment, the cells from herniated disc tissue showed only a weak redifferentiation process in 3D culture. However, propidium iodide/fluorescein diacetate staining documented that 3D assembly of these cells in polyglycolic acid scaffolds allows prolonged culture and high viability. Conclusions Study results suggested a very limited regenerative potential for cells harvested from herniated disc tissue. Further research on 2 major aspects in patient selection is suggested before conducting reasonable clinical trials in this matter: 1) diagnostic strategies to predict the regenerative potential of harvested cells at a radiological or cell biology level, and 2) clinical assessment strategies to elucidate the metabolic state of the targeted disc.

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36

Rosenzweig, Derek, Eric Carelli, Thomas Steffen, Peter Jarzem, and Lisbet Haglund. "3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration." International Journal of Molecular Sciences 16, no. 12 (July 3, 2015): 15118–35. http://dx.doi.org/10.3390/ijms160715118.

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37

Yan, Hui-Shen, Cheng Hang, Shu-Wen Chen, Ke-Ke Wang, and Ping Bo. "Salvianolic acid B combined with mesenchymal stem cells contributes to nucleus pulposus regeneration." Connective Tissue Research 61, no. 5 (May 10, 2019): 435–44. http://dx.doi.org/10.1080/03008207.2019.1611794.

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38

Leung, V. Y., D. M. Aladin, F. Lv, V. Tam, Y. Sun, W. W. Lu, E. X. Wu, K. D. Luk, D. Chan, and K. M. Cheung. "Mesenchymal Stem Cells Mediate Disk Regeneration by Suppression of Fibrosis in Nucleus Pulposus." Global Spine Journal 2, no. 1_suppl (June 2012): s—0032–1319877—s—0032–1319877. http://dx.doi.org/10.1055/s-0032-1319877.

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39

Gloria, Antonio, Assunta Borzacchiello, Filippo Causa, and Luigi Ambrosio. "Rheological Characterization of Hyaluronic Acid Derivatives as Injectable Materials Toward Nucleus Pulposus Regeneration." Journal of Biomaterials Applications 26, no. 6 (December 2010): 745–59. http://dx.doi.org/10.1177/0885328210387174.

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40

Zhang, Hua, Wei Li, YaoHong Wu, Shengquan Zhang, Jie Li, Letian Han, Haoyu Chen, et al. "Effects of Changes in Osmolarity on the Biological Activity of Human Normal Nucleus Pulposus Mesenchymal Stem Cells." Stem Cells International 2022 (April 23, 2022): 1–15. http://dx.doi.org/10.1155/2022/1121064.

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The expansion and maintenance of the NPMSC (nucleus pulposus mesenchymal stem cell) phenotype are considered as potential therapeutic tools for clinical applications in intervertebral disc tissue engineering and regenerative medicine. However, the harsh microenvironment within the intervertebral disc is the main limitation of its regeneration. The osmolarity of the intervertebral disc is higher than that of other tissues, which has an important influence on the biological characteristics of NPMSCs. In this study, we observed the effect of different osmolarities on the biological characteristics of human normal NPMSCs cultured in vitro and explored the role of osmolarity in intervertebral disc degeneration. Our data demonstrated that the change in osmotic pressure has an important effect on the biological activity of NPMSCs, and this effect may occur through the P16INK4A/Rb pathway. This study provides a theoretical basis for the future treatment of intervertebral disc degeneration.

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41

Yang, Fan, Yanbin Zhang, Sheng Liu, Jiheng Xiao, Yuxin He, Zengwu Shao, Yuhui Zhang, Xianyi Cai, and Liming Xiong. "Tunneling Nanotube-Mediated Mitochondrial Transfer Rescues Nucleus Pulposus Cells from Mitochondrial Dysfunction and Apoptosis." Oxidative Medicine and Cellular Longevity 2022 (March 4, 2022): 1–16. http://dx.doi.org/10.1155/2022/3613319.

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Stem cell-based therapy has been indicated to be beneficial for intervertebral disc regeneration. However, the underlying mechanisms have not been fully identified. The present study showed that bone marrow mesenchymal stem cells (BMSCs) donated mitochondria to adjacent nucleus pulposus cells (NPCs) in a coculture system. The mode of mitochondrial transfer between these cells was intercellular tunneling nanotube (TNT), which acted as a transportation expressway for mitochondria. NPCs acquired additional mitochondria from BMSCs in a concentration-dependent manner after rotenone-induced mitochondrial dysfunction in NPCs. Further research demonstrated that TNT-mediated mitochondrial transfer rescued NPCs from mitochondrial dysfunction and apoptosis, which was indicated by the recovery of the mitochondrial respiratory chain, the increase in mitochondrial membrane potential, and the decreases in reactive oxygen species (ROS) levels and apoptosis rates. Furthermore, Miro1, a critical protein that regulates mitochondrial movement, was knocked down in BMSCs and significantly reduced mitochondrial transfer from BMSCs to NPCs. These results suggested that Miro1 depletion inhibited the rescue of NPCs with mitochondrial dysfunction. Taken together, our data shed light on a novel mechanism by which BMSCs rescue impaired NPCs, providing a concrete foundation to study the critical role of intercellular interactions in disc regeneration.

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42

Wu, H., Y. Ding, Y. Sun, Z. Liu, and C. Li. "THERMOSENSITIVE HYDROGEL LOADED WITH ENGINEERED ADIPOSE STEM CELLS FOR THE TREATMENT OF DEGENERATIVE INTERVERTEBRAL DISC." Orthopaedic Proceedings 105-B, SUPP_7 (April 4, 2023): 115. http://dx.doi.org/10.1302/1358-992x.2023.7.115.

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Intervertebral disc degeneration can lead to physical disability and significant pain, while the present therapeutics still fail to biochemically and biomechanically restore the tissue. Stem cell-based therapy in treating intervertebral disc (IVD) degeneration is promising while transplanting cells alone might not be adequate for effective regeneration. Recently, gene modification and 3D-printing strategies represent promising strategies to enhanced therapeutic efficacy of MSC therapy. In this regard, we hypothesized that the combination of thermosensitive chitosan hydrogel and adipose derived stem cells (ADSCs) engineered with modRNA encoding Interleukin − 4 (IL-4) can inhibit inflammation and promote the regeneration of the degenerative IVD.Rat ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IL-4 modRNA engineered ADSCs (named as IL-4-ADSCs) on nucleus pulposus cells.ModRNA transfected mouse ADSCs with high efficiency and the IL-4 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IL-4 protein. In vitro, IL-4-ADSCs induced increased anabolic markers expression of nucleus pulposus cells in inflammation environment compared to untreated ADSCs.These findings collectively supported the therapeutic potential of the combination of thermosensitive chitosan hydrogel and IL-4-ADSCs for intervertebral disc degeneration management. Histological and in vivo validation are now being conducted.

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Kasamkattil, Jesil, Anna Gryadunova, Ivan Martin, Andrea Barbero, Stefan Schären, Olga Krupkova, and Arne Mehrkens. "Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc." International Journal of Molecular Sciences 23, no. 5 (February 25, 2022): 2530. http://dx.doi.org/10.3390/ijms23052530.

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Degenerative disc disease, a painful pathology of the intervertebral disc (IVD), often causes disability and reduces quality of life. Although regenerative cell-based strategies have shown promise in clinical trials, none have been widely adopted clinically. Recent developments demonstrated that spheroid-based approaches might help overcome challenges associated with cell-based IVD therapies. Spheroids are three-dimensional multicellular aggregates with architecture that enables the cells to differentiate and synthesize endogenous ECM, promotes cell-ECM interactions, enhances adhesion, and protects cells from harsh conditions. Spheroids could be applied in the IVD both in scaffold-free and scaffold-based configurations, possibly providing advantages over cell suspensions. This review highlights areas of future research in spheroid-based regeneration of nucleus pulposus (NP) and annulus fibrosus (AF). We also discuss cell sources and methods for spheroid fabrication and characterization, mechanisms related to spheroid fusion, as well as enhancement of spheroid performance in the context of the IVD microenvironment.

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Krouwels, A., J. Popov, S. Plomp, W. Dhert, C. Oner, R. Bank, and L. Creemers. "In Vitro Tissue Regeneration by Human Degenerated Nucleus Pulposus Cells in Hyperosmotic Culture Medium." Global Spine Journal 4, no. 1_suppl (May 2014): s—0034–1376656—s—0034–1376656. http://dx.doi.org/10.1055/s-0034-1376656.

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Cunningham, C. M., A. Srivastava, E. Collin, S. Grad, M. Alini, A. Pandit, and G. Wall. "Cell-Targeting Nanoparticles for Gene Delivery to Nucleus Pulposus Cells for Intervertebral Disk Regeneration." Global Spine Journal 2, no. 1_suppl (June 2012): s—0032–1319998—s—0032–1319998. http://dx.doi.org/10.1055/s-0032-1319998.

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Sun, Zhen, Beier Luo, Zhongyang Liu, Liangliang Huang, Bing Liu, Teng Ma, Bo Gao, et al. "Effect of perfluorotributylamine-enriched alginate on nucleus pulposus cell: Implications for intervertebral disc regeneration." Biomaterials 82 (March 2016): 34–47. http://dx.doi.org/10.1016/j.biomaterials.2015.12.013.

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Gan, Yibo, Pei Li, Liyuan Wang, Xiumei Mo, Lei Song, Yuan Xu, Chen Zhao, et al. "An interpenetrating network-strengthened and toughened hydrogel that supports cell-based nucleus pulposus regeneration." Biomaterials 136 (August 2017): 12–28. http://dx.doi.org/10.1016/j.biomaterials.2017.05.017.

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Tsaryk, Roman, Joana Silva-Correia, Joaquim Miguel Oliveira, Ronald E. Unger, Constantin Landes, Christoph Brochhausen, Shahram Ghanaati, Rui L. Reis, and C. James Kirkpatrick. "Biological performance of cell-encapsulated methacrylated gellan gum-based hydrogels for nucleus pulposus regeneration." Journal of Tissue Engineering and Regenerative Medicine 11, no. 3 (November 5, 2014): 637–48. http://dx.doi.org/10.1002/term.1959.

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Li, Zhen, Gernot Lang, Lindsay S. Karfeld-Sulzer, Kerstin T. Mader, R. Geoff Richards, Franz E. Weber, Chris Sammon, et al. "Heterodimeric BMP-2/7 for nucleus pulposus regeneration-In vitro and ex vivo studies." Journal of Orthopaedic Research 35, no. 1 (July 7, 2016): 51–60. http://dx.doi.org/10.1002/jor.23351.

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Белых, Evgeniy Belykh, Бардонова, Lyudmila Bardonova, Бывальцев, and Vadim Byvaltsev. "BONE MORPHOGENETIC PROTEIN-2 INFLUENCE ON METABOLIC ACTIVITY AND PROTEOGLYCAN SYNTHESIS BY INTERVERTEBRAL DISC CELLS." Бюллетень Восточно-Сибирского научного центра Сибирского отделения Российской академии медицинских наук 1, no. 4 (November 28, 2016): 99–103. http://dx.doi.org/10.12737/22977.

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Modern therapeutic strategies for intervertebral disc repair mainly focus on targeting molecular pathways of extracel-lular matrix degeneration. Anabolic strategies for regeneration are aimed to increase production of major extracellular molecules. Members of TGF-b superfamily proteins, particularly the bone morphogenetic proteins (BMP) have a high regenerative potential regarding the mesenchymal cells. The goal of this study is to study production of proteoglycans by the intervertebral disc cells under the influence of bone morphogenetic protein 2.Material and methods. The experiment was carried out on the cell cultures derived from the annulus fibrosis cells and nucleus pulposus cells of the human intervertebral disc. We studied cell livability, metabolic activity and proteoglycan expression. Cell livability was assessed using the trypan blue staining. Alamar blue test was used for the estimation of metabolic activity. Amount of sulfated glycosaminoglycans was assessed using the assay based on the reaction with 1,9-Dimethylmethylene Blue.Results. Cultivation with bone morphogenetic protein 2 in different concentrations did not decrease livability of the cells. Study cell cultures with application of bone morphogenetic protein 2 in different concentrations showed significant increase in metabolic activity and proteoglycan synthesis by the annulus fibrosis cells. Despite the relative increase in the number of the nucleus pulposus cells treated with the bone morphogenetic protein 2, the differences in metabolic and synthetic activity compared with control group was not significant. Conclusion. The bone morphogenetic protein 2 has an anabolic effect towards the intervertebral disc cells, particularly in the production of proteoglycans by the annulus fibrosis cells.

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