Current Research Status and Progress of Stem Cells Therapy for Degenerative Intervertebral Disc Regeneration_Journal of Biomedical Engineering

Authors：

XIEGuangyou ,  LUFurong , YANGHaitao

Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;

Corresponding author：

LUFurong, Email: frankyang119@126.com

Keywords：

intervertebral discs; degeneration; stem cell; tissue regeneration

DOI：

10.7507/1001-5515.20140269

Video：

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Low back pain caused by intervertebral disc degeneration is a common clinical chronic disease. The regenerative ability of intervertebral disc tissue is extremely poor. Meanwhile, current treating methods can not fundamentally solve such problems. With the increasing awareness of the mechanism of disc degeneration and the rapid development of the fields of cellular and molecular biology, gene and materials engineering, using stem cells and tissue engineering technology to slow down or reverse the progress of disc degeneration may become possible. The author reviewed the application of stem cells for treating degenerative discs from present researching status and concepts for the future in the combination of researches reported both at home and abroad.

Citation： XIEGuangyou, LUFurong, YANGHaitao. Current Research Status and Progress of Stem Cells Therapy for Degenerative Intervertebral Disc Regeneration. Journal of Biomedical Engineering, 2014, 31(6): 1419-1422. doi: 10.7507/1001-5515.20140269 Copy

1.	KEPLER C K, PONNAPPAN R K, TANNOURY C A, et al. The molecular basis of intervertebral disc degeneration[J]. Spine J, 2013, 13(3):318-330.
2.	HUGHES S P, FREEMONT A J, HUKINS D W, et al. The pathogenesis of degeneration of the intervertebral disc and emerging therapies in the management of back pain[J]. J Bone Joint Surg Br, 2012, 94(10):1298-1304.
3.	HUANG S, TAM V, CHEUNG K M, et al. Stem cell-based approaches for intervertebral disc regeneration[J]. Curr Stem Cell Res Ther, 2011, 6(4):317-326.
4.	BERGKNUT N, SMOLDERS L A, GRINWIS G C, et al. Intervertebral disc degeneration in the dog. Part 1:Anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration[J]. Vet J, 2013, 195(3):282-291.
5.	BERGKNUT N, MEIJ B P, HAGMAN R, et al. Intervertebral disc disease in dogs-part 1:a new histological grading scheme for classification of intervertebral disc degeneration in dogs[J]. Vet J, 2013, 195(2):156-163.
6.	BOUBRIAK O A, WATSON N, SIVAN S S, et al. Factors regulating viable cell density in the intervertebral disc:blood supply in relation to disc height[J]. J Anat, 2013, 222(3):341-348.
7.	BERGKNUT N, RUTGES J P, KRANENBURG H J, et al. The dog as an animal model for intervertebral disc degeneration?[J]. Spine (Phila Pa 1976), 2012, 37(5):351-358.
8.	RISBUD M V, GUTTAPALLI A, TSAI T T, et al. Evidence for skeletal progenitor cells in the degenerate human intervertebral disc[J]. Spine (Phila Pa 1976), 2007, 32(23):2537-2544.
9.	FENG G, YANG X, SHANG H, et al. Multipotential differentiation of human anulus fibrosus cells:an in vitro study[J]. J Bone Joint Surg Am, 2010, 92(3):675-685.
10.	CHUN H J, KIM Y S, KIM B K, et al. Transplantation of human adipose-derived stem cells in a rabbit model of traumatic degeneration of lumbar discs[J]. World Neurosurg, 2012, 78(3-4):364-371.
11.	蒋新华,陈建宇,蔡兆熙,等.SPIO标记脂肪干细胞移植退变椎间盘内的MRI活体示踪[J].中国组织工程研究与临床康复,2011,15(40):7515-7519.
12.	GANEY T, HUTTON W C, MOSELEY T, et al. Intervertebral disc repair using adipose tissue-derived stem and regenerative cells:experiments in a canine model[J]. Spine (Phila Pa 1976), 2009, 34(21):2297-2304.
13.	JEONG J H, LEE J H, JIN E S, et al. Regeneration of intervertebral discs in a rat disc degeneration model by implanted adipose-tissue-derived stromal cells[J]. Acta Neurochir (Wien), 2010, 152(10):1771-1777.
14.	FANG Z, YANG Q, LUO W, et al. Differentiation of GFP-Bcl-2-engineered mesenchymal stem cells towards a nucleus pulposus-like phenotype under hypoxia in vitro[J]. Biochem Biophys Res Commun, 2013, 432(3):444-450.
15.	KORECKI C L, TABOAS J M, TUAN R S, et al. Notochordal cell conditioned medium stimulates mesenchymal stem cell differentiation toward a young nucleus pulposus phenotype[J]. Stem Cell Res Ther, 2010, 1(2):18.
16.	ANDERSON D G, MARKOVA D, AN H S, et al. Human umbilical cord blood-derived mesenchymal stem cells in the cultured rabbit intervertebral disc:a novel cell source for disc repair[J]. Am J Phys Med Rehabil, 2013, 92(5):420-429.
17.	张彦男,邵增务,吴永超,等.脊索细胞促进骨髓间充质干细胞增殖及定向诱导分化的研究[J].中华实验外科杂志,2012,29(7):1271-1274.
18.	CHEN S, EMERY S E, PEI M. Coculture of synovium-derived stem cells and nucleus pulposus cells in serum-free defined medium with supplementation of transforming growth factor-beta1:a potential application of tissue-specific stem cells in disc regeneration[J]. Spine (Phila Pa 1976), 2009, 34(12):1272-1280.
19.	WATANABE T, SAKAI D, YAMAMOTO Y, et al. Human nucleus pulposus cells significantly enhanced biological properties in a coculture system with direct cell-to-cell contact with autologous mesenchymal stem cells[J]. J Orthop Res, 2010, 28(5):623-630.
20.	YAMAMOTO Y, MOCHIDA J, SAKAI D, et al. Upregulation of the viability of nucleus pulposus cells by bone marrow-derived stromal cells:significance of direct cell-to-cell contact in coculture system[J]. Spine (Phila Pa 1976), 2004, 29(14):1508-1514.
21.	STRASSBURG S, RICHARDSON S M, FREEMONT A J, et al. Co-culture induces mesenchymal stem cell differentiation and modulation of the degenerate human nucleus pulposus cell phenotype[J]. Regen Med, 2010, 5(5):701-711.
22.	SAKAI D, NAKAMURA Y, NAKAI T, et al. Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc[J]. Nat Commun, 2012, 3:1264.
23.	ALLON A A, AUROUER N, YOO B B, et al. Structured coculture of stem cells and disc cells prevent disc degeneration in a rat model[J]. Spine J, 2010, 10(12):1089-1097.
24.	HIYAMA A, MOCHIDA J, IWASHINA T, et al. Transplantation of mesenchymal stem cells in a canine disc degeneration model[J]. J Orthop Res, 2008, 26(5):589-600.
25.	OROZCO L, SOLER R, MORERA C, et al. Intervertebral disc repair by autologous mesenchymal bone marrow cells:a pilot study[J]. Transplantation, 2011, 92(7):822-828.
26.	PROLOGO J D, PIRASTEH A, TENLEY N, et al. Percutaneous image-guided delivery for the transplantation of mesenchymal stem cells in the setting of degenerated intervertebral discs[J]. J Vasc Interv Radiol, 2012, 23(8):1084-1088.e6.
27.	YOSHIKAWA T, UEDA Y, MIYAZAKI K, et al. Disc regeneration therapy using marrow mesenchymal cell transplantation:a report of two case studies[J]. Spine (Phila Pa 1976), 2010, 35(11):E475-E480.
28.	VADALÀ G, SOWA G, HUBERT M, et al. Mesenchymal stem cells injection in degenerated intervertebral disc:cell leakage may induce osteophyte formation[J]. J Tissue Eng Regen Med, 2012, 6(5):348-355.

1. KEPLER C K, PONNAPPAN R K, TANNOURY C A, et al. The molecular basis of intervertebral disc degeneration[J]. Spine J, 2013, 13(3):318-330.
2. HUGHES S P, FREEMONT A J, HUKINS D W, et al. The pathogenesis of degeneration of the intervertebral disc and emerging therapies in the management of back pain[J]. J Bone Joint Surg Br, 2012, 94(10):1298-1304.
3. HUANG S, TAM V, CHEUNG K M, et al. Stem cell-based approaches for intervertebral disc regeneration[J]. Curr Stem Cell Res Ther, 2011, 6(4):317-326.
4. BERGKNUT N, SMOLDERS L A, GRINWIS G C, et al. Intervertebral disc degeneration in the dog. Part 1:Anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration[J]. Vet J, 2013, 195(3):282-291.
5. BERGKNUT N, MEIJ B P, HAGMAN R, et al. Intervertebral disc disease in dogs-part 1:a new histological grading scheme for classification of intervertebral disc degeneration in dogs[J]. Vet J, 2013, 195(2):156-163.
6. BOUBRIAK O A, WATSON N, SIVAN S S, et al. Factors regulating viable cell density in the intervertebral disc:blood supply in relation to disc height[J]. J Anat, 2013, 222(3):341-348.
7. BERGKNUT N, RUTGES J P, KRANENBURG H J, et al. The dog as an animal model for intervertebral disc degeneration?[J]. Spine (Phila Pa 1976), 2012, 37(5):351-358.
8. RISBUD M V, GUTTAPALLI A, TSAI T T, et al. Evidence for skeletal progenitor cells in the degenerate human intervertebral disc[J]. Spine (Phila Pa 1976), 2007, 32(23):2537-2544.
9. FENG G, YANG X, SHANG H, et al. Multipotential differentiation of human anulus fibrosus cells:an in vitro study[J]. J Bone Joint Surg Am, 2010, 92(3):675-685.
10. CHUN H J, KIM Y S, KIM B K, et al. Transplantation of human adipose-derived stem cells in a rabbit model of traumatic degeneration of lumbar discs[J]. World Neurosurg, 2012, 78(3-4):364-371.
11. 蒋新华,陈建宇,蔡兆熙,等.SPIO标记脂肪干细胞移植退变椎间盘内的MRI活体示踪[J].中国组织工程研究与临床康复,2011,15(40):7515-7519.
12. GANEY T, HUTTON W C, MOSELEY T, et al. Intervertebral disc repair using adipose tissue-derived stem and regenerative cells:experiments in a canine model[J]. Spine (Phila Pa 1976), 2009, 34(21):2297-2304.
13. JEONG J H, LEE J H, JIN E S, et al. Regeneration of intervertebral discs in a rat disc degeneration model by implanted adipose-tissue-derived stromal cells[J]. Acta Neurochir (Wien), 2010, 152(10):1771-1777.
14. FANG Z, YANG Q, LUO W, et al. Differentiation of GFP-Bcl-2-engineered mesenchymal stem cells towards a nucleus pulposus-like phenotype under hypoxia in vitro[J]. Biochem Biophys Res Commun, 2013, 432(3):444-450.
15. KORECKI C L, TABOAS J M, TUAN R S, et al. Notochordal cell conditioned medium stimulates mesenchymal stem cell differentiation toward a young nucleus pulposus phenotype[J]. Stem Cell Res Ther, 2010, 1(2):18.
16. ANDERSON D G, MARKOVA D, AN H S, et al. Human umbilical cord blood-derived mesenchymal stem cells in the cultured rabbit intervertebral disc:a novel cell source for disc repair[J]. Am J Phys Med Rehabil, 2013, 92(5):420-429.
17. 张彦男,邵增务,吴永超,等.脊索细胞促进骨髓间充质干细胞增殖及定向诱导分化的研究[J].中华实验外科杂志,2012,29(7):1271-1274.
18. CHEN S, EMERY S E, PEI M. Coculture of synovium-derived stem cells and nucleus pulposus cells in serum-free defined medium with supplementation of transforming growth factor-beta1:a potential application of tissue-specific stem cells in disc regeneration[J]. Spine (Phila Pa 1976), 2009, 34(12):1272-1280.
19. WATANABE T, SAKAI D, YAMAMOTO Y, et al. Human nucleus pulposus cells significantly enhanced biological properties in a coculture system with direct cell-to-cell contact with autologous mesenchymal stem cells[J]. J Orthop Res, 2010, 28(5):623-630.
20. YAMAMOTO Y, MOCHIDA J, SAKAI D, et al. Upregulation of the viability of nucleus pulposus cells by bone marrow-derived stromal cells:significance of direct cell-to-cell contact in coculture system[J]. Spine (Phila Pa 1976), 2004, 29(14):1508-1514.
21. STRASSBURG S, RICHARDSON S M, FREEMONT A J, et al. Co-culture induces mesenchymal stem cell differentiation and modulation of the degenerate human nucleus pulposus cell phenotype[J]. Regen Med, 2010, 5(5):701-711.
22. SAKAI D, NAKAMURA Y, NAKAI T, et al. Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc[J]. Nat Commun, 2012, 3:1264.
23. ALLON A A, AUROUER N, YOO B B, et al. Structured coculture of stem cells and disc cells prevent disc degeneration in a rat model[J]. Spine J, 2010, 10(12):1089-1097.
24. HIYAMA A, MOCHIDA J, IWASHINA T, et al. Transplantation of mesenchymal stem cells in a canine disc degeneration model[J]. J Orthop Res, 2008, 26(5):589-600.
25. OROZCO L, SOLER R, MORERA C, et al. Intervertebral disc repair by autologous mesenchymal bone marrow cells:a pilot study[J]. Transplantation, 2011, 92(7):822-828.
26. PROLOGO J D, PIRASTEH A, TENLEY N, et al. Percutaneous image-guided delivery for the transplantation of mesenchymal stem cells in the setting of degenerated intervertebral discs[J]. J Vasc Interv Radiol, 2012, 23(8):1084-1088.e6.
27. YOSHIKAWA T, UEDA Y, MIYAZAKI K, et al. Disc regeneration therapy using marrow mesenchymal cell transplantation:a report of two case studies[J]. Spine (Phila Pa 1976), 2010, 35(11):E475-E480.
28. VADALÀ G, SOWA G, HUBERT M, et al. Mesenchymal stem cells injection in degenerated intervertebral disc:cell leakage may induce osteophyte formation[J]. J Tissue Eng Regen Med, 2012, 6(5):348-355.

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