A systematic review of the safety and efficacy of mesenchymal stem cells for disc degeneration: Insights and future directions for regenerative therapeutics

Stem Cells and Development

Volumn 23, Issue 21, 2014, Pages 2553-2567

  Yim, Rita Lok Hay ^a   Lee, Juliana Tsz Yan ^a   Bow, Cora H ^a   Meij, Björn ^b   Leung, Victor ^a   Cheung, Kenneth M C ^a   Vavken, Patrick ^c,d,e   Samartzis, Dino ^a  

^a UNIVERSITY OF HONG KONG   (Hong Kong)

^b UTRECHT UNIVERSITY   (Netherlands)

^c HARVARD MEDICAL SCHOOL   (United States)

^d HARVARD CENTER FOR POPULATION AND DEVELOPMENT STUDIES   (United States)

^e UNIVERSITY OF BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ATELOCOLLAGEN; COLLAGEN TYPE 2; PROTEOGLYCAN; TRANSCRIPTION FACTOR SOX9;

ADIPOSE DERIVED STEM CELL; BONE MARROW DERIVED MESENCHYMAL STEM CELL; CONTROLLED CLINICAL TRIAL (TOPIC); HEMATOPOIETIC STEM CELL; HUMAN; INTERVERTEBRAL DISK; INTERVERTEBRAL DISK DEGENERATION; MESENCHYMAL STEM CELL TRANSPLANTATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; REGENERATIVE ABILITY; REGENERATIVE MEDICINE; REVIEW; SAFETY; SYNOVIOCYTE; SYSTEMATIC REVIEW; TISSUE REPAIR; ANIMAL; FORECASTING; INTERVERTEBRAL DISC DEGENERATION; PATHOPHYSIOLOGY; PROCEDURES; REGENERATION; TREATMENT OUTCOME; TRENDS;

ANIMALS; FORECASTING; HUMANS; INTERVERTEBRAL DISC DEGENERATION; MESENCHYMAL STEM CELL TRANSPLANTATION; REGENERATION; REGENERATIVE MEDICINE; TREATMENT OUTCOME;

EID: 84913615100     PISSN: 15473287     EISSN: 15578534     Source Type: Journal    
DOI: 10.1089/scd.2014.0203     Document Type: Review

References (71)

1. Vos T, AD Flaxman, M Naghavi, R Lozano, C Michaud, M Ezzati, K Shibuya, JA Salomon, S Abdalla, et al. (2012). 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 380:2163-2196.
2. Deyo RA and YJ Tsui-Wu. (1987). Descriptive epidemiology of low-back pain and its related medical care in the United States. Spine (Phila Pa 1976) 12:264-268.
3. Karppinen J, FH Shen, KD Luk, GB Andersson, KM Cheung and D Samartzis. (2011). Management of degenerative disk disease and chronic low back pain. Orthop Clin North Am 42:513-528, viii.
4. Shen FH, D Samartzis and GB Andersson. (2006). Nonsurgical management of acute and chronic low back pain. J Am Acad Orthop Surg 14:477-487.
5. Cheung KM, J Karppinen, D Chan, DW Ho, YQ Song, P Sham, KS Cheah, JC Leong and KD Luk. (2009). Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-Three individuals. Spine (Phila Pa 1976) 34:934-940.
6. de Schepper EI, J Damen, JB van Meurs, AZ Ginai, M Popham, A Hofman, BW Koes and SM Bierma-Zeinstra. (2010). The association between lumbar disc degeneration and low back pain: The influence of age, gender, and individual radiographic features. Spine (Phila Pa 1976) 35:531-536.
7. Samartzis D, J Karppinen, D Chan, KD Luk and KM Cheung. (2010). The association of disc degeneration based on magnetic resonance imaging and the presence of low back pain. In: World Forum for Spine Research: Intervertebral Disc. Montreal, Canada.
8. Samartzis D, J Karppinen, F Mok, DY Fong, KD Luk and KM Cheung. (2011). A population-based study of juvenile disc degeneration and its association with overweight and obesity, low back pain, and diminished functional status. J Bone Joint Surg Am 93:662-670.
9. Takatalo J, J Karppinen, J Niinimaki, S Taimela, S Nayha, P Mutanen, RB Sequeiros, E Kyllonen and O Tervonen. (2011). Does lumbar disc degeneration on MRI associate with low back symptom severity in young Finnish adults? Spine (Phila Pa 1976) 36:2180-2189.
10. Kjaer P, C Leboeuf-Yde, L Korsholm, JS Sorensen and T Bendix. (2005). Magnetic resonance imaging and low back pain in adults: A diagnostic imaging study of 40-year-old men and women. Spine (Phila Pa 1976) 30:1173-1180.
11. Visuri T, J Ulaska, M Eskelin and P Pulkkinen. (2005). Narrowing of lumbar spinal canal predicts chronic low back pain more accurately than intervertebral disc degeneration: A magnetic resonance imaging study in young Finnish male conscripts. Mil Med 170:926-930.
12. Paajanen H, M Erkintalo, T Kuusela, S Dahlstrom and M Kormano. (1989). Magnetic resonance study of disc degeneration in young low-back pain patients. Spine (Phila Pa 1976) 14:982-985.
13. Paajanen H, M Erkintalo, R Parkkola, J Salminen and M Kormano. (1997). Age-dependent correlation of low-back pain and lumbar disc regeneration. Arch Orthop Trauma Surg 116:106-107.
14. Chou D, D Samartzis, C Bellabarba, A Patel, KDK Luk, JM Schenk-Kisser and AC Skelly. (2011). Degenerative MRI findings in patients with chronic low back pain: A systematic review. Spine (Phila Pa 1976) 36:S43-S53.
15. Adams MA, BJ Freeman, HP Morrison, IW Nelson and P Dolan. (2000). Mechanical initiation of intervertebral disc degeneration. Spine (Phila Pa 1976) 25:1625-1636.
16. Urban JP and JF McMullin. (1988). Swelling pressure of the lumbar intervertebral discs: Influence of age, spinal level, composition, and degeneration. Spine (Phila Pa 1976) 13:179-187.
17. Biyani A and GBJ Andersson. (2004). Low back pain: Pathophysiology and management. J Am Acad Orthop Surg 12:106-115.
18. Adams MA and PJ Roughley. (2006). What is intervertebral disc degeneration, and what causes it?. Spine (Phila Pa 1976) 31:2151-2161.
19. Urban JP, S Holm, A Maroudas and A Nachemson. (1982). Nutrition of the intervertebral disc: Effect of fluid flow on solute transport. Clin Orthop Relat Res:296-302.
20. Urban JP and S Roberts. (2003). Degeneration of the intervertebral disc. Arthritis Res Ther 5:120-130.
21. Urban JP and CP Winlove. (2007). Pathophysiology of the intervertebral disc and the challenges for MRI. J Magn Reson Imaging 25:419-432.
22. Fujiwara A, HS An, TH Lim and VM Haughton. (2001). Morphologic changes in the lumbar intervertebral foramen due to flexion-extension, lateral bending, and axial rotation: An in vitro anatomic and biomechanical study. Spine (Phila Pa 1976) 26:876-882.
23. Fujiwara A, K Tamai, HS An, T Kurihashi, TH Lim, H Yoshida and K Saotome. (2000). The relationship between disc degeneration, facet joint osteoarthritis, and stability of the degenerative lumbar spine. J Spinal Disord 13:444-450.
24. Fujiwara A, K Tamai, M Yamato, HS An, H Yoshida, K Saotome and A Kurihashi. (1999). The relationship between facet joint osteoarthritis and disc degeneration of the lumbar spine: An MRI study. Eur Spine J 8:396-401.
25. Siepe CJ, F Heider, K Wiechert, W Hitzl, B Ishak and MH Mayer. (2014). Mid-To long-Term results of total lumbar disc replacement: A prospective analysis with 5-To 10-year follow-up. Spine J. DOI: 10.1016/j.spinee.2013.08.028.
26. Mannion AF, JI Brox and JC Fairbank. (2013). Comparison of spinal fusion and nonoperative treatment in patients with chronic low back pain: Long-Term follow-up of three randomized controlled trials. Spine J 13:1438-1448.
27. Punt IM, VM Visser, LW van Rhijn, SM Kurtz, J Antonis, GW Schurink and A van Ooij. (2008). Complications and reoperations of the SB Charite lumbar disc prosthesis: Experience in 75 patients. Eur Spine J 17:36-43.
28. An HS, K Takegami, H Kamada, CM Nguyen, EJ Thonar, K Singh, GB Andersson and K Masuda. (2005). Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine (Phila Pa 1976) 30:25-31; discussion 31-32.
29. Bae WC and K Masuda. (2011). Emerging technologies for molecular therapy for intervertebral disk degeneration. Orthop Clin North Am 42:585-601, ix.
30. Masuda K, TR Oegema, Jr. and HS An. (2004). Growth factors and treatment of intervertebral disc degeneration. Spine (Phila Pa 1976) 29:2757-2769.
31. Masuda K. (2008). Biological repair of the degenerated intervertebral disc by the injection of growth factors. Eur Spine J 17 Suppl 4:441-451.
32. Meisel HJ, V Siodla, T Ganey, Y Minkus,WC Hutton and OJ Alasevic. (2007). Clinical experience in cell-based therapeutics: Disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc. Biomol Eng 24:5-21.
33. Yoon ST and NM Patel. (2006). Molecular therapy of the intervertebral disc. Eur Spine J 15 Suppl 3:S379-S388.
34. Woods BI, N Vo, G Sowa and JD Kang. (2011). Gene therapy for intervertebral disk degeneration. Orthop Clin North Am 42:563-574, ix.
35. Orozco L, R Soler, C Morera, M Alberca, A Sanchez and J Garcia-Sancho. (2011). Intervertebral disc repair by autologous mesenchymal bone marrow cells: A pilot study. Transplantation 92:822-828.
36. Yoshikawa TMD, YMD Ueda, KMD Miyazaki, MMD Koizumi and YMD Takakura. (2010). Disc regeneration therapy using marrow mesenchymal cell transplantation: A report of two case studies. Spine (Phila Pa 1976) 35:E475-E480.
37. Zhang Y-G, X Guo, P Xu, L-L Kang and J Li. (2005). Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans. Clin Orthop Relat Res 430:219-226.
38. Chou AI, AT Reza and SB Nicoll. (2008). Distinct intervertebral disc cell populations adopt similar phenotypes in threedimensional culture. Tissue Eng Part A 14:2079-2087.
39. Leung V, D Chan and K Cheung. (2006). Regeneration of intervertebral disc by mesenchymal stem cells: Potentials, limitations, and future direction. Eur Spine J 15:406-413.
40. Jeong J, J Lee, E Jin, J Min, S Jeon and K Choi. (2010). Regeneration of intervertebral discs in a rat disc degeneration model by implanted adipose-Tissue-derived stromal cells. Acta Neurochir (Wien) 152:1771-1777.
41. Rovira J, J Cid, G Gutierrez-Garcia, A Pereira, F Fernandez-Aviles, L Rosinol, C Martinez, E Carreras, A Urbano, M Rovira and M Lozano. (2013). Fatal immune hemolytic anemia following allogeneic stem cell transplantation: Report of 2 cases and review of literature. Transfus Med Rev 27:166-170.
42. Vadala G, G Sowa, M Hubert, LG Gilbertson, V Denaro and JD Kang. (2011). Mesenchymal stem cells injection in degenerated intervertebral disc: Cell leakage may induce osteophyte formation. J Tissue Eng Regen Med 6:348-355.
43. Amariglio N, A Hirshberg, BW Scheithauer, Y Cohen, R Loewenthal, L Trakhtenbrot, N Paz, M Koren-Michowitz, D Waldman and L Leider-Trejo. (2009). Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med 6:e1000029.
44. Moher D, A Liberati, J Tetzlaff and DG Altman. (2009). Preferred reporting items for systematic reviews and metaanalyses: The PRISMA statement. Int J Surg 8:339-341.
45. Jadad AR, RA Moore, D Carroll, C Jenkinson, DJM Reynolds, DJ Gavaghan and HJ McQuay. (1996). Assessing the quality of reports of randomized clinical trials: Is blinding necessary?. Control Clin Trials 17:1-12.
46. Hee HT, HD Ismail, CT Lim, JCH Goh and HK Wong. (2010). Effects of implantation of bone marrow mesenchymal stem cells, disc distraction and combined therapy on reversing degeneration of the intervertebral disc. J Bone Joint Surg Br 92-B:726-736.
47. Bendtsen M, CE Bunger, X Zou, C Foldager and HS Jørgensen. (2011). Autologous stem cell therapy maintains vertebral blood flow and contrast diffusion through the endplate in experimental intervertebral disc degeneration. Spine (Phila Pa 1976) 36:E373-E379.
48. Crevensten G, AJL Walsh, D Ananthakrishnan, P Page, GM Wahba, JC Lotz and S Berven. (2004). Intervertebral disc cell therapy for regeneration: Mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 32:430-434.
49. Yang F, VYL Leung, KDK Luk, D Chan and KMC Cheung. (2009). Mesenchymal stem cells arrest intervertebral disc degeneration through chondrocytic differentiation and stimulation of endogenous cells. Mol Ther 17:1959-1966.
50. Jeong J, E Jin, J Min, S Jeon, C-S Park, H Kim and K Choi. (2009). Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat. Cytotechnology 59:55-64.
51. Allon AA, N Aurouer, BB Yoo, EC Liebenberg, Z Buser and JC Lotz. (2010). Structured coculture of stem cells and disc cells prevent disc degeneration in a rat model. Spine J 10:1089-1097.
52. Wei A, H Tao, SA Chung, H Brisby, DD Ma and AD Diwan. (2009). The fate of transplanted xenogeneic bone marrow-derived stem cells in rat intervertebral discs. J Orthop Res 27:374-379.
53. Feng G, X Zhao, H Liu, H Zhang, X Chen, R Shi, X Liu, X Zhao, W Zhang and B Wang. (2011). Transplantation of mesenchymal stem cells and nucleus pulposus cells in a degenerative disc model in rabbits: A comparison of 2 cell types as potential candidates for disc regeneration. J Neurosurg Spine 14:322-329.
54. Sakai D, J Mochida, T Iwashina, A Hiyama, H Omi, M Imai, T Nakai, K Ando and T Hotta. (2006). Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 27:335-345.
55. Sakai D, J Mochida, Y Yamamoto, T Nomura, M Okuma, K Nishimura, T Nakai, K Ando and T Hotta. (2003). Transplantation of mesenchymal stem cells embedded in Atelocollagen-gel to the intervertebral disc: A potential therapeutic model for disc degeneration. Biomaterials 24:3531-3541.
56. Sakai DMD, JMD Mochida, TMD Iwashina, TMD Watanabe, T Nakai, KMD Ando and TMD Hotta. (2005). Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: Potential and limitations for stem cell therapy in disc regeneration. Spine (Phila Pa 1976) 30:2379-2387.
57. Ho G,VYLLeung,KMCCheung andDChan. (2008). Effect of severity of intervertebral disc injury on mesenchymal stem cell-based regeneration. Connect Tissue Res 49:15-21.
58. Sobajima S, G Vadala, A Shimer, JS Kim, LG Gilbertson and JD Kang. (2008). Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J 8:888-896.
59. Yang H, J Wu, J Liu, M Ebraheim, S Castillo, X Liu, T Tang and NA Ebraheim. (2010). Transplanted mesenchymal stem cells with pure fibrinous gelatin-Transforming growth factor-[beta]1 decrease rabbit intervertebral disc degeneration. Spine J 10:802-810.
60. Serigano K, D Sakai, A Hiyama, F Tamura, M Tanaka and J Mochida. (2010). Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. J Orthop Res 28:1267-1275.
61. Henriksson HBM, TMD Svanvik, MLMS Jonsson, MB Hagman, MP Horn, AMDP Lindahl and HMDP Brisby. (2009). Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model. Spine (Phila Pa 1976) 34:141-148.
62. Acosta F, L Metz, H Adkisson, J Liu, E Carruthers-Liebenberg, C Milliman, M Maloney and J Lotz. (2011). Porcine intervertebral disc repair using allogeneic juvenile articular chondrocytes or mesenchymal stem cells. Tissue Eng Part A 17:3045-3055.
63. Hiyama A, J Mochida, T Iwashina, H Omi, T Watanabe, K Serigano, F Tamura and D Sakai. (2008). Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res 26:589-600.
64. Ghosh P, R Moore, B Vernon-Roberts, T Goldschlager, D Pascoe, A Zannettino, S Gronthos and S Itescu. (2012). Immunoselected STRO-3 + mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs. J Neurosurg Spine 16:479-488.
65. Ganey TP, WCD Hutton, TP Moseley, MMD Hedrick and H-JMDP Meisel. (2009). Intervertebral disc repair using adipose tissue-derived stem and regenerative cells: Experiments in a canine model. Spine (Phila Pa 1976) 34:2297-2304.
66. Miyamoto T, T Muneta, T Tabuchi, K Matsumoto, H Saito, K Tsuji and I Sekiya. (2010). Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits. Arthritis Res Ther 12:R206.
67. Song M, J Heo, J-Y Chun, HS Bae, JW Kang, H Kang, YM Cho, SW Kim, D-M Shin and M-S Choo. (2013). The paracrine effects of mesenchymal stem cells stimulate the regeneration capacity of endogenous stem cells in the repair of a bladder-outlet-obstruction-induced overactive bladder. Stem CellsDev 23:654-663.
68. Smith LJ, NL Nerurkar, K-S Choi, BD Harfe and DM Elliott. (2011). Degeneration and regeneration of the intervertebral disc: Lessons from development. Dis Model Mech 4:31-41.
69. Risbud MV, TP Schaer and IM Shapiro. (2010). Toward an understanding of the role of notochordal cells in the adult intervertebral disc: From discord to accord. Dev Dyn 239:2141-2148.
70. Chen J, WYan and L Setton. (2006). Molecular phenotypes of notochordal cells purified from immature nucleus pulposus. Eur Spine J 15:303-311.
71. Bergknut NP, JPHJMDP Rutges, H-JCDVM Kranenburg, LAB Smolders, RP Hagman, H-JB Smidt, A-SDVMP Lagerstedt, LCP Penning, GDVMP Voorhout, et al. (2012). The dog as an animal model for intervertebral disc degeneration?. Spine (Phila Pa 1976) 37:351-358.