Cartilage Endplate-Derived Stem Cells for Regeneration of Intervertebral Disc Degeneration: An Analytic Study

References

• Andersson GB. Epidemiological features of chronic low-back pain. Lancet. 1999;354(9178):581–585. doi:10.1016/S0140-6736(99)01312-4
   PubMed Web of Science ®Google Scholar
• Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–2196. doi:10.1016/S0140-6736(12)61729-2
   PubMed Web of Science ®Google Scholar
• Walker BF. The prevalence of low back pain: a systematic review of the literature from 1966 to 1998. J Spinal Disord. 2000;13(3):205–217. doi:10.1097/00002517-200006000-00003
   PubMedGoogle Scholar
• Hoy D, March L, Brooks P, et al. The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 2014;73(6):968–974. doi:10.1136/annrheumdis-2013-204428
   PubMed Web of Science ®Google Scholar
• Lyu FJ, Cheung KM, Zheng Z, Wang H, Sakai D, Leung VY. IVD progenitor cells: a new horizon for understanding disc homeostasis and repair. Nat Rev Rheumatol. 2019;15(2):102–112. doi:10.1038/s41584-018-0154-x
   PubMed Web of Science ®Google Scholar
• Roh JS, Teng AL, Yoo JU, Davis J, Furey C, Bohlman HH. Degenerative disorders of the lumbar and cervical spine. Orthop Clin North Am. 2005;36(3):255–262. doi:10.1016/j.ocl.2005.01.007
   PubMed Web of Science ®Google Scholar
• Dagenais S, Caro J, Haldeman S. A systematic review of low back pain cost of illness studies in the United States and internationally. Spine J. 2008;8(1):8–20. doi:10.1016/j.spinee.2007.10.005
   PubMed Web of Science ®Google Scholar
• Liu Y, Li Y, Nan LP, et al. Insights of stem cell-based endogenous repair of intervertebral disc degeneration. World J Stem Cells. 2020;12(4):266–276. doi:10.4252/wjsc.v12.i4.266
   PubMed Web of Science ®Google Scholar
• Du Y, Wang Z, Wu Y, Liu C, Zhang L, Hu B. Intervertebral disc stem/progenitor cells: a promising “Seed” for intervertebral disc regeneration. Stem Cells Int. 2021;2021:2130727. doi:10.1155/2021/2130727
   PubMed Web of Science ®Google Scholar
• Hu B, He R, Ma K, et al. Intervertebral disc-derived stem/progenitor cells as a promising cell source for intervertebral disc regeneration. Stem Cells Int. 2018;2018:7412304. doi:10.1155/2018/7412304
   PubMed Web of Science ®Google Scholar
• Hadjipavlou AG, Tzermiadianos MN, Bogduk N, Zindrick MR. The pathophysiology of disc degeneration: a critical review. J Bone Joint Surg Br. 2008;90(10):1261–1270. doi:10.1302/0301-620X.90B10.20910
   PubMedGoogle Scholar
• Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine. 2006;31(18):2151–2161. doi:10.1097/01.brs.0000231761.73859.2c
   PubMed Web of Science ®Google Scholar
• Li B, Yang Y, Wang L, Liu G, Hu B. Stem cell therapy and exercise for treatment of intervertebral disc degeneration. Stem Cells Int. 2021;2021:7982333. doi:10.1155/2021/7982333
   PubMed Web of Science ®Google Scholar
• Sakai D, Andersson GB. Stem cell therapy for intervertebral disc regeneration: obstacles and solutions. Nat Rev Rheumatol. 2015;11(4):243–256. doi:10.1038/nrrheum.2015.13
   PubMed Web of Science ®Google Scholar
• Huang S, Tam V, Cheung KM, et al. Stem cell-based approaches for intervertebral disc regeneration. Curr Stem Cell Res Ther. 2011;6(4):317–326. doi:10.2174/157488811797904335
   PubMed Web of Science ®Google Scholar
• Vadala G, Ambrosio L, Russo F, Papalia R, Denaro V. Stem cells and intervertebral disc regeneration overview-what they can and can’t do. Int J Spine Surg. 2021;15(s1):40–53. doi:10.14444/8054
   PubMedGoogle Scholar
• Magnier C, Boiron O, Wendling-Mansuy S, Chabrand P, Deplano V. Nutrient distribution and metabolism in the intervertebral disc in the unloaded state: a parametric study. J Biomech. 2009;42(2):100–108. doi:10.1016/j.jbiomech.2008.10.034
   PubMed Web of Science ®Google Scholar
• Huang YC, Urban JP, Luk KD. Intervertebral disc regeneration: do nutrients lead the way? Nat Rev Rheumatol. 2014;10(9):561–566. doi:10.1038/nrrheum.2014.91
   PubMed Web of Science ®Google Scholar
• Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebral disc. Spine. 2004;29(23):2700–2709. doi:10.1097/01.brs.0000146499.97948.52
   PubMed Web of Science ®Google Scholar
• Peng B, Hou S, Shi Q, Jia L. The relationship between cartilage end-plate calcification and disc degeneration: an experimental study. Chin Med J. 2001;114(3):308–312.
   PubMed Web of Science ®Google Scholar
• Roberts S, Urban JP, Evans H, Eisenstein SM. Transport properties of the human cartilage endplate in relation to its composition and calcification. Spine. 1996;21(4):415–420. doi:10.1097/00007632-199602150-00003
   PubMed Web of Science ®Google Scholar
• Benneker LM, Heini PF, Alini M, Anderson SE, Ito K. 2004 Young Investigator Award Winner: vertebral endplate marrow contact channel occlusions and intervertebral disc degeneration. Spine. 2005;30(2):167–173. doi:10.1097/01.brs.0000150833.93248.09
   PubMed Web of Science ®Google Scholar
• Rajasekaran S, Venkatadass K, Naresh Babu J, Ganesh K, Shetty AP. Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated discs: results from in-vivo serial post-contrast MRI studies in 365 human lumbar discs. Eur Spine J. 2008;17(5):626–643. doi:10.1007/s00586-008-0645-6
   PubMed Web of Science ®Google Scholar
• Ariga K, Miyamoto S, Nakase T, et al. The relationship between apoptosis of endplate chondrocytes and aging and degeneration of the intervertebral disc. Spine. 2001;26(22):2414–2420. doi:10.1097/00007632-200111150-00004
   PubMed Web of Science ®Google Scholar
• Rajasekaran S, Babu JN, Arun R, Armstrong BR, Shetty AP, Murugan S. ISSLS prize winner: a study of diffusion in human lumbar discs: a serial magnetic resonance imaging study documenting the influence of the endplate on diffusion in normal and degenerate discs. Spine. 2004;29(23):2654–2667. doi:10.1097/01.brs.0000148014.15210.64
   PubMed Web of Science ®Google Scholar
• de Sousa EB, Casado PL, Moura Neto V, Duarte ME, Aguiar DP. Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and therapeutic perspectives. Stem Cell Res Ther. 2014;5(5):112. doi:10.1186/scrt501
   PubMedGoogle Scholar
• Jiang D, Yang S, Gao P, et al. Combined effect of ligament stem cells and umbilical-cord-blood-derived CD34+ cells on ligament healing. Cell Tissue Res. 2015;362(3):587–595. doi:10.1007/s00441-015-2250-4
   PubMed Web of Science ®Google Scholar
• Ito Y, Fitzsimmons JS, Sanyal A, Mello MA, Mukherjee N, O’Driscoll SW. Localization of chondrocyte precursors in periosteum. Osteoarthritis Cartilage. 2001;9(3):215–223. doi:10.1053/joca.2000.0378
   PubMed Web of Science ®Google Scholar
• Debnath S, Yallowitz AR, McCormick J, et al. Discovery of a periosteal stem cell mediating intramembranous bone formation. Nature. 2018;562(7725):133–139. doi:10.1038/s41586-018-0554-8
   PubMed Web of Science ®Google Scholar
• Williams R, Khan IM, Richardson K, et al. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS One. 2010;5(10):e13246. doi:10.1371/journal.pone.0013246
   PubMed Web of Science ®Google Scholar
• Yin H, Price F, Rudnicki MA. Satellite cells and the muscle stem cell niche. Physiol Rev. 2013;93(1):23–67. doi:10.1152/physrev.00043.2011
   PubMed Web of Science ®Google Scholar
• Zhang Y, Hu Y, Wang W, et al. Current Progress in the Endogenous Repair of Intervertebral Disk Degeneration Based on Progenitor Cells. Front Bioeng Biotechnol. 2020;8:629088. doi:10.3389/fbioe.2020.629088
   PubMed Web of Science ®Google Scholar
• Liu LT, Huang B, Li CQ, Zhuang Y, Wang J, Zhou Y. Characteristics of stem cells derived from the degenerated human intervertebral disc cartilage endplate. PLoS One. 2011;6(10):e26285. doi:10.1371/journal.pone.0026285
   PubMed Web of Science ®Google Scholar
• Huang B, Liu LT, Li CQ, et al. Study to determine the presence of progenitor cells in the degenerated human cartilage endplates. Eur Spine J. 2012;21(4):613–622. doi:10.1007/s00586-011-2039-4
   PubMed Web of Science ®Google Scholar
• Chen BL, Guo JB, Zhang HW, et al. Surgical versus non-operative treatment for lumbar disc herniation: a systematic review and meta-analysis. Clin Rehabil. 2018;32(2):146–160. doi:10.1177/0269215517719952
   PubMed Web of Science ®Google Scholar
• Meisel HJ, Agarwal N, Hsieh PC, et al. Cell therapy for treatment of intervertebral disc degeneration: a systematic review. Global Spine J. 2019;9(1 Suppl):39S–52S. doi:10.1177/2192568219829024
   PubMed Web of Science ®Google Scholar
• Gou S, Oxentenko SC, Eldrige JS, et al. Stem cell therapy for intervertebral disk regeneration. Am J Phys Med Rehabil. 2014;93(11 Suppl 3):S122–S131. doi:10.1097/PHM.0000000000000152
   PubMed Web of Science ®Google Scholar
• Epstein NE. Adjacent level disease following lumbar spine surgery: a review. Surg Neurol Int. 2015;6(Suppl 24):S591–S599. doi:10.4103/2152-7806.170432
   PubMedGoogle Scholar
• Krut Z, Pelled G, Gazit D, Gazit Z. Stem cells and exosomes: new therapies for intervertebral disc degeneration. Cells. 2021;10(9):2241. doi:10.3390/cells10092241
   PubMed Web of Science ®Google Scholar
• Binch ALA, Fitzgerald JC, Growney EA, Barry F. Cell-based strategies for IVD repair: clinical progress and translational obstacles. Nat Rev Rheumatol. 2021;17(3):158–175. doi:10.1038/s41584-020-00568-w
   PubMed Web of Science ®Google Scholar
• Ma K, Chen S, Li Z, et al. Mechanisms of endogenous repair failure during intervertebral disc degeneration. Osteoarthritis Cartilage. 2019;27(1):41–48. doi:10.1016/j.joca.2018.08.021
   PubMed Web of Science ®Google Scholar
• Wu H, Zeng X, Yu J, et al. Comparison of nucleus pulposus stem/progenitor cells isolated from degenerated intervertebral discs with umbilical cord derived mesenchymal stem cells. Exp Cell Res. 2017;361(2):324–332. doi:10.1016/j.yexcr.2017.10.034
   PubMed Web of Science ®Google Scholar
• Johnson WE, Stephan S, Roberts S. The influence of serum, glucose and oxygen on intervertebral disc cell growth in vitro: implications for degenerative disc disease. Arthritis Res Ther. 2008;10(2):R46. doi:10.1186/ar2405
   PubMed Web of Science ®Google Scholar
• Lee CH, Lee FY, Tarafder S, et al. Harnessing endogenous stem/progenitor cells for tendon regeneration. J Clin Invest. 2015;125(7):2690–2701. doi:10.1172/JCI81589
   PubMed Web of Science ®Google Scholar
• Clouet J, Fusellier M, Camus A, Le Visage C, Guicheux J. Intervertebral disc regeneration: from cell therapy to the development of novel bioinspired endogenous repair strategies. Adv Drug Deliv Rev. 2019;146:306–324. doi:10.1016/j.addr.2018.04.017
   PubMed Web of Science ®Google Scholar
• Zhang W, Sun T, Li Y, et al. Application of stem cells in the repair of intervertebral disc degeneration. Stem Cell Res Ther. 2022;13(1):70. doi:10.1186/s13287-022-02745-y
   PubMed Web of Science ®Google Scholar
• Wells K, Littell JH. Study quality assessment in systematic reviews of research on intervention effects. Res Soc Work Pract. 2009;19(1):52–62. doi:10.1177/1049731508317278
   Web of Science ®Google Scholar
• Shin RL, Lee CW, Shen OY, Xu H, Lee OK, Jones EA. The crosstalk between mesenchymal stem cells and macrophages in bone regeneration: a systematic review. Stem Cells Int. 2021;2021:8835156. doi:10.1155/2021/8835156
   PubMed Web of Science ®Google Scholar
• Lin Y, Tang Z, Jin L, Yang Y. The expression and regulatory roles of long non-coding RNAs in periodontal ligament cells: a systematic review. Biomolecules. 2022;12(2):304. doi:10.3390/biom12020304
   PubMed Web of Science ®Google Scholar
• Xu H, Lee CW, Wang YF, et al. The role of paracrine regulation of mesenchymal stem cells in the crosstalk with macrophages in musculoskeletal diseases: a systematic review. Front Bioeng Biotechnol. 2020;8:587052. doi:10.3389/fbioe.2020.587052
   PubMed Web of Science ®Google Scholar
• Xu HT, Lee CW, Li MY, Wang YF, Yung PS, Lee OK. The shift in macrophages polarisation after tendon injury: a systematic review. J Orthop Translat. 2020;21:24–34. doi:10.1016/j.jot.2019.11.009
   PubMed Web of Science ®Google Scholar
• Martelli AJ, Machado RA, Martelli DRB, Neves LTD, Martelli Junior H. The 100 most-cited papers in oral medicine and pathology. Braz Oral Res. 2020;35:e020.
   PubMed Web of Science ®Google Scholar
• Garcovich D, Marques Martinez L, Adobes Martin M. Citation classics in paediatric dentistry: a bibliometric study on the 100 most-cited articles. Eur Arch Paediatr Dent. 2020;21(2):249–261. doi:10.1007/s40368-019-00483-z
   PubMed Web of Science ®Google Scholar
• Xiong CJ, Huang B, Zhou Y, et al. Macrophage migration inhibitory factor inhibits the migration of cartilage end plate-derived stem cells by reacting with CD74. PLoS One. 2012;7(8):e43984. doi:10.1371/annotation/a5edef40-e46d-4810-9008-dbda429ccc2c
   PubMed Web of Science ®Google Scholar
• Wang H, Zhou Y, Huang B, et al. Utilization of stem cells in alginate for nucleus pulposus tissue engineering. Tissue Eng Part A. 2014;20(5–6):908–920. doi:10.1089/ten.tea.2012.0703
   PubMed Web of Science ®Google Scholar
• Shang J, Fan X, Shangguan L, Liu H, Zhou Y. Global gene expression profiling and alternative splicing events during the chondrogenic differentiation of human cartilage endplate-derived stem cells. Biomed Res Int. 2015;2015:604972. doi:10.1155/2015/604972
   PubMed Web of Science ®Google Scholar
• Feng C, Zhang Y, Yang M, Huang B, Zhou Y. Collagen-derived N-acetylated proline-glycine-proline in intervertebral discs modulates CXCR1/2 expression and activation in cartilage endplate stem cells to induce migration and differentiation toward a pro-inflammatory phenotype. Stem Cells. 2015;33(12):3558–3568. doi:10.1002/stem.2200
   PubMed Web of Science ®Google Scholar
• Wang H, Zhou Y, Chu TW, et al. Distinguishing characteristics of stem cells derived from different anatomical regions of human degenerated intervertebral discs. Eur Spine J. 2016;25(9):2691–2704. doi:10.1007/s00586-016-4522-4
   PubMed Web of Science ®Google Scholar
• Yao Y, Shang J, Song W, Deng Q, Liu H, Zhou Y. Global profiling of the gene expression and alternative splicing events during hypoxia-regulated chondrogenic differentiation in human cartilage endplate-derived stem cells. Genomics. 2016;107(5):170–177. doi:10.1016/j.ygeno.2016.03.003
   PubMed Web of Science ®Google Scholar
• Shang J, Wang H, Fan X, Shangguan L, Liu H. A genome wide analysis of alternative splicing events during the osteogenic differentiation of human cartilage endplate-derived stem cells. Mol Med Rep. 2016;14(2):1389–1396. doi:10.3892/mmr.2016.5359
   PubMed Web of Science ®Google Scholar
• Yao Y, Deng Q, Song W, et al. MIF plays a key role in regulating tissue-specific chondro-osteogenic differentiation fate of human cartilage endplate stem cells under hypoxia. Stem Cell Rep. 2016;7(2):249–262. doi:10.1016/j.stemcr.2016.07.003
   PubMed Web of Science ®Google Scholar
• Liu S, Liang H, Lee SM, Li Z, Zhang J, Fei Q. Isolation and identification of stem cells from degenerated human intervertebral discs and their migration characteristics. Acta Biochim Biophys Sin. 2017;49(2):101–109. doi:10.1093/abbs/gmw121
   Google Scholar
• He Z, Pu L, Yuan C, Jia M, Wang J. Nutrition deficiency promotes apoptosis of cartilage endplate stem cells in a caspase-independent manner partially through upregulating BNIP3. Acta Biochim Biophys Sin. 2017;49(1):25–32. doi:10.1093/abbs/gmw111
   Google Scholar
• Yao Y, Deng Q, Sun C, Song W, Liu H, Zhou Y. A genome-wide analysis of the gene expression profiles and alternative splicing events during the hypoxia-regulated osteogenic differentiation of human cartilage endplate-derived stem cells. Mol Med Rep. 2017;16(2):1991–2001. doi:10.3892/mmr.2017.6846
   PubMed Web of Science ®Google Scholar
• Liang L, Li X, Li D, et al. The characteristics of stem cells in human degenerative intervertebral disc. Medicine. 2017;96(25):e7178. doi:10.1097/MD.0000000000007178
   PubMed Web of Science ®Google Scholar
• Yao Y, Song W, Deng Q, et al. General regulatory effects of hypoxia on human cartilage endplate-derived stem cells: a genomewide analysis of differential gene expression and alternative splicing events. Mol Med Rep. 2017;16(3):3001–3009. doi:10.3892/mmr.2017.6907
   PubMed Web of Science ®Google Scholar
• He Z, Jia M, Yu Y, Yuan C, Wang J. Roles of SDF-1/CXCR4 axis in cartilage endplate stem cells mediated promotion of nucleus pulposus cells proliferation. Biochem Biophys Res Commun. 2018;506(1):94–101. doi:10.1016/j.bbrc.2018.10.069
   PubMed Web of Science ®Google Scholar
• Yuan C, Pu L, He Z, Wang J. BNIP3/Bcl-2-mediated apoptosis induced by cyclic tensile stretch in human cartilage endplate-derived stem cells. Exp Ther Med. 2018;15(1):235–241. doi:10.3892/etm.2017.5372
   PubMed Web of Science ®Google Scholar
• Sun C, Lan W, Li B, et al. Glucose regulates tissue-specific chondro-osteogenic differentiation of human cartilage endplate stem cells via O-GlcNAcylation of Sox9 and Runx2. Stem Cell Res Ther. 2019;10(1):357. doi:10.1186/s13287-019-1440-5
   PubMed Web of Science ®Google Scholar
• Zuo R, Wang Y, Li J, et al. Rapamycin induced autophagy inhibits inflammation-mediated endplate degeneration by enhancing Nrf2/Keap1 signaling of cartilage endplate stem cells. Stem Cells. 2019;37(6):828–840. doi:10.1002/stem.2999
   PubMed Web of Science ®Google Scholar
• Luo L, Gong J, Zhang H, et al. Cartilage endplate stem cells transdifferentiate into nucleus pulposus cells via autocrine exosomes. Front Cell Dev Biol. 2021;9:648201. doi:10.3389/fcell.2021.648201
   PubMed Web of Science ®Google Scholar
• Guan Y, Sun C, Zou F, et al. Carbohydrate sulfotransferase 3 (CHST3) overexpression promotes cartilage endplate-derived stem cells (CESCs) to regulate molecular mechanisms related to repair of intervertebral disc degeneration by rat nucleus pulposus. J Cell Mol Med. 2021;25(13):6006–6017. doi:10.1111/jcmm.16440
   PubMed Web of Science ®Google Scholar
• Luo L, Jian X, Sun H, et al. Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy. Stem Cells. 2021;39(4):467–481. doi:10.1002/stem.3322
   PubMed Web of Science ®Google Scholar
• Chen D, Jiang X. Exosomes-derived miR-125-5p from cartilage endplate stem cells regulates autophagy and ECM metabolism in nucleus pulposus by targeting SUV38H1. Exp Cell Res. 2022;414(1):113066. doi:10.1016/j.yexcr.2022.113066
   PubMed Web of Science ®Google Scholar
• Luo L, Gong J, Wang Z, et al. Injectable cartilage matrix hydrogel loaded with cartilage endplate stem cells engineered to release exosomes for non-invasive treatment of intervertebral disc degeneration. Bioact Mater. 2022;15:29–43. doi:10.1016/j.bioactmat.2021.12.007
   PubMed Web of Science ®Google Scholar
• Zhang Y, Liu C, Li Y, Xu H. Mechanism of the mitogen-activated protein kinases/mammalian target of rapamycin pathway in the process of cartilage endplate stem cell degeneration induced by tension load. Global Spine J. 2023;13(8):2396–2408. doi:10.1177/21925682221085226
   PubMed Web of Science ®Google Scholar
• Chen Y, Chen Q, Zhong M, Xu C, Wu Y, Chen R. miR-637 inhibits osteogenic differentiation of human intervertebral disc cartilage endplate stem cells by targeting WNT5A. J Invest Surg. 2022;35(6):1313–1321. doi:10.1080/08941939.2022.2050857
   PubMed Web of Science ®Google Scholar
• Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–317. doi:10.1080/14653240600855905
   PubMed Web of Science ®Google Scholar
• Lin L, Jia Z, Zhao Y, et al. Use of limiting dilution method for isolation of nucleus pulposus mesenchymal stem/progenitor cells and effects of plating density on biological characteristics and plasticity. Biomed Res Int. 2017;2017:9765843. doi:10.1155/2017/9765843
   PubMed Web of Science ®Google Scholar
• Sekiya I, Larson BL, Smith JR, Pochampally R, Cui JG, Prockop DJ. Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem Cells. 2002;20(6):530–541. doi:10.1634/stemcells.20-6-530
   PubMed Web of Science ®Google Scholar
• Feng G, Yang X, Shang H, et al. Multipotential differentiation of human anulus fibrosus cells: an in vitro study. J Bone Joint Surg Am. 2010;92(3):675–685. doi:10.2106/JBJS.H.01672
   PubMedGoogle Scholar
• Sakai D, Nakamura Y, Nakai T, et al. Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc. Nat Commun. 2012;3:1264. doi:10.1038/ncomms2226
   PubMed Web of Science ®Google Scholar
• Li FC, Zhang N, Chen WS, Chen QX. Endplate degeneration may be the origination of the vacuum phenomenon in intervertebral discs. Med Hypotheses. 2010;75(2):169–171. doi:10.1016/j.mehy.2010.02.012
   PubMed Web of Science ®Google Scholar
• Antoniou J, Goudsouzian NM, Heathfield TF, et al. The human lumbar endplate. Evidence of changes in biosynthesis and denaturation of the extracellular matrix with growth, maturation, aging, and degeneration. Spine. 1996;21(10):1153–1161. doi:10.1097/00007632-199605150-00006
   PubMed Web of Science ®Google Scholar
• Zhu LL, Wu LY, Yew DT, Fan M. Effects of hypoxia on the proliferation and differentiation of NSCs. Mol Neurobiol. 2005;31(1–3):231–242.
   PubMed Web of Science ®Google Scholar
• Chen W, Zhuo Y, Duan D, Lu M. Effects of hypoxia on differentiation of mesenchymal stem cells. Curr Stem Cell Res Ther. 2020;15(4):332–339. doi:10.2174/1574888X14666190823144928
   PubMed Web of Science ®Google Scholar
• Vadala G, Ambrosio L, Russo F, Papalia R, Denaro V. Interaction between mesenchymal stem cells and intervertebral disc microenvironment: from cell therapy to tissue engineering. Stem Cells Int. 2019;2019:2376172. doi:10.1155/2019/2376172
   PubMed Web of Science ®Google Scholar
• Wang F, Shi R, Cai F, Wang YT, Wu XT. Stem cell approaches to intervertebral disc regeneration: obstacles from the disc microenvironment. Stem Cells Dev. 2015;24(21):2479–2495. doi:10.1089/scd.2015.0158
   PubMed Web of Science ®Google Scholar
• Takahashi H, Suguro T, Okazima Y, Motegi M, Okada Y, Kakiuchi T. Inflammatory cytokines in the herniated disc of the lumbar spine. Spine. 1996;21(2):218–224. doi:10.1097/00007632-199601150-00011
   PubMed Web of Science ®Google Scholar
• Shamji MF, Setton LA, Jarvis W, et al. Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues. Arthritis Rheum. 2010;62(7):1974–1982. doi:10.1002/art.27444
   PubMed Web of Science ®Google Scholar
• Walsh DA, McWilliams DF, Turley MJ, et al. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. Rheumatology. 2010;49(10):1852–1861. doi:10.1093/rheumatology/keq188
   PubMed Web of Science ®Google Scholar
• Nerlich AG, Schaaf R, Walchli B, Boos N. Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs. Eur Spine J. 2007;16(4):547–555. doi:10.1007/s00586-006-0213-x
   PubMed Web of Science ®Google Scholar
• O’Connell GD, Leach JK, Klineberg EO. Tissue engineering a biological repair strategy for lumbar disc herniation. Biores Open Access. 2015;4(1):431–445. doi:10.1089/biores.2015.0034
   PubMedGoogle Scholar
• Buckley CT, Hoyland JA, Fujii K, Pandit A, Iatridis JC, Grad S. Critical aspects and challenges for intervertebral disc repair and regeneration-Harnessing advances in tissue engineering. JOR Spine. 2018;1(3):e1029. doi:10.1002/jsp2.1029
   PubMedGoogle Scholar
• Melrose J. Strategies in regenerative medicine for intervertebral disc repair using mesenchymal stem cells and bioscaffolds. Regen Med. 2016;11(7):705–724. doi:10.2217/rme-2016-0069
   PubMed Web of Science ®Google Scholar
• Zhang Y, Bi J, Huang J, Tang Y, Du S, Li P. Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. Int J Nanomedicine. 2020;15:6917–6934. doi:10.2147/IJN.S264498
   PubMed Web of Science ®Google Scholar
• Sakai D, Mochida J, Yamamoto Y, et al. Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials. 2003;24(20):3531–3541. doi:10.1016/S0142-9612(03)00222-9
   PubMed Web of Science ®Google Scholar
• Drazin D, Rosner J, Avalos P, Acosta F. Stem cell therapy for degenerative disc disease. Adv Orthop. 2012;2012:961052. doi:10.1155/2012/961052
   PubMedGoogle Scholar
• Haufe SM, Mork AR. Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev. 2006;15(1):136–137. doi:10.1089/scd.2006.15.136
   PubMed Web of Science ®Google Scholar
• Sakai D, Schol J. Cell therapy for intervertebral disc repair: clinical perspective. J Orthop Translat. 2017;9:8–18. doi:10.1016/j.jot.2017.02.002
   PubMed Web of Science ®Google Scholar