International Orthopaedics

, Volume 43, Issue 4, pp 1027–1036 | Cite as

Autogenic mesenchymal stem cells for intervertebral disc regeneration

  • Filippo MiglioriniEmail author
  • Björn Rath
  • Markus Tingart
  • Alice Baroncini
  • Valentin Quack
  • Jörg Eschweiler



A systematic review of the literature was conducted to clarify the outcomes of autologous mesenchymal stem cells (MSC) injections for the regeneration of the intervertebral disc (IVD).


The following databases were accessed: PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar bibliographic databases. Articles including previous or planned surgical interventions were excluded. Only articles reporting percutaneous autologous MSC injection to regenerate IVD in humans were included. We referred to the Coleman Methodology Score for the methodological quality assessment. The statistical analysis was performed using Review Manager Software 5.3.


After the databases search and cross-references of the bibliographies, seven studies were included in the present work. The funnel plot detected low risk of publication bias. The Coleman Methodology Score reported a good result, scoring 61.07 points. A total of 98 patients were enrolled, with 122 treated levels. All the patients underwent conservative therapies prior to injection. A remarkable improvement in the quality of life were reported after the treatment. The average Oswestry Disability Index (ODI) improved from “severe disability” to “minimal disability” at one year follow-up. The visual analogue scale (VAS) showed an improvement of ca. 30% at one year follow-up. Only one case of herniated nucleus pulposus was reported. No other adverse events at the aspiration or injection site were observed.


This systematic review of the literature proved MSC injection to be a safe and feasible option for intervertebral disc regeneration in the early-degeneration stage patients. Irrespective of the source of the MSCs, an overall clinical and radiological improvement of the patients has been evidenced, as indeed a very low complication rate during the follow-up.


Mesenchymal stem cells Regenerative medicine Intervertebral disc degeneration Low back pain Spine 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Not required for this type of study


  1. 1.
    Golob AL, Wipf JE (2014) Low back pain. Med Clin North Am 98(3):405–428. Google Scholar
  2. 2.
    Vergroesen PP, Kingma I, Emanuel KS, Hoogendoorn RJ, Welting TJ, van Royen BJ, van Dieen JH, Smit TH (2015) Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthr Cartil 23(7):1057–1070. Google Scholar
  3. 3.
    Mochida J, Sakai D, Nakamura Y, Watanabe T, Yamamoto Y, Kato S (2015) Intervertebral disc repair with activated nucleus pulposus cell transplantation: a three-year, prospective clinical study of its safety. Eur Cell Mater 29:202–212 discussion 212Google Scholar
  4. 4.
    Murtagh R, Castellvi AE (2014) Motion preservation surgery in the spine. Neuroimaging Clin N Am 24(2):287–294. Google Scholar
  5. 5.
    Errico TJ (2004) Why a mechanical disc? Spine J 4(Suppl 6):151S–157SGoogle Scholar
  6. 6.
    Soroceanu A, Diebo BG, Burton D, Smith JS, Deviren V, Shaffrey C, Kim HJ, Mundis G, Ames C, Errico T, Bess S, Hostin R, Hart R, Schwab F, Lafage V, International Spine Study G (2015) Radiographical and implant-related complications in adult spinal deformity surgery: incidence, patient risk factors, and impact on health-related quality of life. Spine (Phila Pa 1976) 40(18):1414–1421. Google Scholar
  7. 7.
    Fineberg SJ, Oglesby M, Patel AA, Pelton MA, Singh K (2013) Outcomes of cervical spine surgery in teaching and non-teaching hospitals. Spine (Phila Pa 1976) 38(13):1089–1096. Google Scholar
  8. 8.
    Guerin P, El Fegoun AB, Obeid I, Gille O, Lelong L, Luc S, Bourghli A, Cursolle JC, Pointillart V, Vital JM (2012) Incidental durotomy during spine surgery: incidence, management and complications. A retrospective review. Injury 43(4):397–401. Google Scholar
  9. 9.
    Li H, Zou X, Bunger C (2001) Gene therapy and spinal disorders. Int Orthop 25(1):1–4Google Scholar
  10. 10.
    Terzic A, Pfenning MA, Gores GJ, Harper CM Jr (2015) Regenerative medicine build-out. Stem Cells Transl Med 4(12):1373–1379. Google Scholar
  11. 11.
    Tabar V, Studer L (2014) Pluripotent stem cells in regenerative medicine: challenges and recent progress. Nat Rev Genet 15(2):82–92. Google Scholar
  12. 12.
    Dulak J, Szade K, Szade A, Nowak W, Jozkowicz A (2015) Adult stem cells: hopes and hypes of regenerative medicine. Acta Biochim Pol 62(3):329–337. Google Scholar
  13. 13.
    Longo UG, Rizzello G, Berton A, Ciuffreda M, Migliorini F, Khan WS, Denaro V (2013) Potential of adipose derived stem cells in orthopaedic surgery. Curr Stem Cell Res Ther 8(6):418–421Google Scholar
  14. 14.
    Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H (2014) Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop 38(9):1811–1818. Google Scholar
  15. 15.
    Gruber HE, Hanley EN Jr (2002) Ultrastructure of the human intervertebral disc during aging and degeneration: comparison of surgical and control specimens. Spine (Phila Pa 1976) 27(8):798–805Google Scholar
  16. 16.
    Kraus P, Lufkin T (2017) Implications for a stem cell regenerative medicine based approach to human intervertebral disk degeneration. Front Cell Dev Biol 5:17. Google Scholar
  17. 17.
    Grunhagen TWG, Soukane DM et al (2006) Nutrient supply and intervertebral disc metabolism. J Bone Joint Surg Am 88(suppl 2):30–35Google Scholar
  18. 18.
    Bibby SRJD, Ripley RM et al (2005) Metabolism of the intervertebral disc: effects of low levels of oxygen, glucose, and pH on rates of energy metabolism of bovine nucleus pulposus cells. Spine (Phila Pa 1976) 30:487–496Google Scholar
  19. 19.
    Urban JP (2002) The role of the physicochemical environment in determining disc cell behaviour. Biochem Soc Trans 30:858–864Google Scholar
  20. 20.
    Leung VY, Aladin DM, Lv F, Tam V, Sun Y, Lau RY, Hung SC, Ngan AH, Tang B, Lim CT, Wu EX, Luk KD, Lu WW, Masuda K, Chan D, Cheung KM (2014) Mesenchymal stem cells reduce intervertebral disc fibrosis and facilitate repair. Stem Cells 32(8):2164–2177. Google Scholar
  21. 21.
    Song K, Gu T, Shuang F, Tang J, Ren D, Qin J, Hou S (2015) Adipose-derived stem cells improve the viability of nucleus pulposus cells in degenerated intervertebral discs. Mol Med Rep 12(3):4664–4668. Google Scholar
  22. 22.
    Erwin WM, Islam D, Eftekarpour E, Inman RD, Karim MZ, Fehlings MG (2013) Intervertebral disc-derived stem cells: implications for regenerative medicine and neural repair. Spine (Phila Pa 1976) 38(3):211–216. Google Scholar
  23. 23.
    Shi R, Wang F, Hong X, Wang YT, Bao JP, Cai F, Wu XT (2015) The presence of stem cells in potential stem cell niches of the intervertebral disc region: an in vitro study on rats. Eur Spine J 24(11):2411–2424. Google Scholar
  24. 24.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. Google Scholar
  25. 25.
    Howick J CI, Glasziou P, Greenhalgh T, Carl Heneghan, Liberati A, Moschetti I, Phillips B, Thornton H, Goddard O, Hodgkinson M (2011) The 2011 Oxford CEBM levels of evidence. Oxford Centre for Evidence-Based Medicine. Available at Accessed on July 2018
  26. 26.
    Wright SMHJ (2003) Introducing levels of evidence to the journal. J Bone Joint Surg 85-A:1–3Google Scholar
  27. 27.
    Fairbank JC (2014) Oswestry Disability Index. J Neurosurg Spine 20(2):239–241. Google Scholar
  28. 28.
    Pinski JM, Boakye LA, Murawski CD, Hannon CP, Ross KA, Kennedy JG (2016) Low level of evidence and methodologic quality of clinical outcome studies on cartilage repair of the ankle. Arthroscopy 32(1):214–222 e211. Google Scholar
  29. 29.
    Nyland J, Causey B, Wera J, Krupp R, Tate D, Gupta A (2017) Distal biceps brachii tendon repair: a systematic review of patient outcome determination using modified Coleman methodology score criteria. Knee Surg Sports Traumatol Arthrosc 25(7):2293–2297. Google Scholar
  30. 30.
    Longo UG, Berton A, Salvatore G, Migliorini F, Ciuffreda M, Nazarian A, Denaro V (2016) Medial patellofemoral ligament reconstruction combined with bony procedures for patellar instability: current indications, outcomes, and complications. Arthroscopy 32(7):1421–1427. Google Scholar
  31. 31.
    Yoshikawa T, Ueda Y, Miyazaki K, Koizumi M, Takakura Y (2010) Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine (Phila Pa 1976) 35(11):E475–E480. Google Scholar
  32. 32.
    Kumar H, Ha DH, Lee EJ, Park JH, Shim JH, Ahn TK, Kim KT, Ropper AE, Sohn S, Kim CH, Thakor DK, Lee SH, Han IB (2017) Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study. Stem Cell Res Ther 8(1):262. Google Scholar
  33. 33.
    Noriega DC, Ardura F, Hernandez-Ramajo R, Martin-Ferrero MA, Sanchez-Lite I, Toribio B, Alberca M, Garcia V, Moraleda JM, Sanchez A, Garcia-Sancho J (2017) Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: a randomized controlled trial. Transplantation 101(8):1945–1951. Google Scholar
  34. 34.
    Centeno C, Markle J, Dodson E, Stemper I, Williams CJ, Hyzy M, Ichim T, Freeman M (2017) Treatment of lumbar degenerative disc disease-associated radicular pain with culture-expanded autologous mesenchymal stem cells: a pilot study on safety and efficacy. J Transl Med 15(1):197. Google Scholar
  35. 35.
    Elabd C, Centeno CJ, Schultz JR, Lutz G, Ichim T, Silva FJ (2016) Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: a long-term safety and feasibility study. J Transl Med 14:253. Google Scholar
  36. 36.
    Orozco L, Soler R, Morera C, Alberca M, Sanchez A, Garcia-Sancho J (2011) Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 92(7):822–828. Google Scholar
  37. 37.
    Pettine KA, Murphy MB, Suzuki RK, Sand TT (2015) Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells 33(1):146–156. Google Scholar
  38. 38.
    Ahmed ST, Ranjan R, Saha SB, Singh B (2014) Lumbar hernia: a diagnostic dilemma. BMJ Case Rep.
  39. 39.
    Coskun Benlidayi I, Basaran S, Seydaoglu G (2016) Lumbosacral morphology in lumbar disc herniation: a “chicken and egg” issue. Acta Orthop Traumatol Turc 50(3):346–350. Google Scholar
  40. 40.
    Daghighi MH, Pouriesa M, Maleki M, Fouladi DF, Pezeshki MZ, Mazaheri Khameneh R, Bazzazi AM (2014) Migration patterns of herniated disc fragments: a study on 1,020 patients with extruded lumbar disc herniation. Spine J 14(9):1970–1977. Google Scholar
  41. 41.
    Pettine KA, Suzuki RK, Sand TT, Murphy MB (2017) Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. Int Orthop 41(10):2097–2103. Google Scholar
  42. 42.
    Centeno CJ, Al-Sayegh H, Freeman MD, Smith J, Murrell WD, Bubnov R (2016) A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. Int Orthop 40(8):1755–1765. Google Scholar
  43. 43.
    Adams MA, Dolan P, Hutton WC (1986) The stages of disc degeneration as revealed by discograms. J Bone Joint Surg Br 68(1):36–41Google Scholar
  44. 44.
    Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N (2001) Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976) 26(17):1873–1878Google Scholar
  45. 45.
    Modic MT, Ross JS (1991) Magnetic resonance imaging in the evaluation of low back pain. Orthop Clin North Am 22(2):283–301Google Scholar
  46. 46.
    Li XC, Wu YH, Bai XD, Ji W, Guo ZM, Wang CF, He Q, Ruan DK (2016) BMP7-based functionalized self-assembling peptides protect nucleus pulposus-derived stem cells from apoptosis in vitro. Tissue Eng Part A 22(19–20):1218–1228. Google Scholar
  47. 47.
    Gou S, Oxentenko SC, Eldrige JS, Xiao L, Pingree MJ, Wang Z, Perez-Terzic C, Qu W (2014) Stem cell therapy for intervertebral disk regeneration. Am J Phys Med Rehabil 93(11 Suppl 3):S122–S131. Google Scholar
  48. 48.
    Allon AA, Butcher K, Schneider RA, Lotz JC (2012) Structured bilaminar coculture outperforms stem cells and disc cells in a simulated degenerate disc environment. Spine (Phila Pa 1976) 37(10):813–818. Google Scholar
  49. 49.
    Maidhof R, Rafiuddin A, Chowdhury F, Jacobsen T, Chahine NO (2017) Timing of mesenchymal stem cell delivery impacts the fate and therapeutic potential in intervertebral disc repair. J Orthop Res 35(1):32–40. Google Scholar
  50. 50.
    Strassburg S, Hodson NW, Hill PI, Richardson SM, Hoyland JA (2012) Bi-directional exchange of membrane components occurs during co-culture of mesenchymal stem cells and nucleus pulposus cells. PLoS One 7(3):e33739. Google Scholar
  51. 51.
    Shim EK, Lee JS, Kim DE, Kim SK, Jung BJ, Choi EY, Kim CS (2016) Autogenous mesenchymal stem cells from the vertebral body enhance intervertebral disc regeneration via paracrine interaction: an in vitro pilot study. Cell Transplant 25(10):1819–1832. Google Scholar
  52. 52.
    Yang W, Yu XH, Wang C, He WS, Zhang SJ, Yan YG, Zhang J, Xiang YX, Wang WJ (2015) Interleukin-1beta in intervertebral disk degeneration. Clin Chim Acta 450:262–272. Google Scholar
  53. 53.
    Kim DW, Chun HJ, Lee SK (2015) Percutaneous needle puncture technique to create a rabbit model with traumatic degenerative disk disease. World Neurosurg 84(2):438–445. Google Scholar
  54. 54.
    Battie MC, Lazary A, Fairbank J, Eisenstein S, Heywood C, Brayda-Bruno M, Varga PP, McCall I (2014) Disc degeneration-related clinical phenotypes. Eur Spine J 23(Suppl 3):S305–S314. Google Scholar
  55. 55.
    Teraguchi M, Yoshimura N, Hashizume H, Muraki S, Yamada H, Minamide A, Oka H, Ishimoto Y, Nagata K, Kagotani R, Takiguchi N, Akune T, Kawaguchi H, Nakamura K, Yoshida M (2014) Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study. Osteoarthr Cartil 22(1):104–110. Google Scholar
  56. 56.
    Szpalski M (2006) Presidential address of the 32nd annual meeting of the International Society for the Study of the Lumbar Spine: spine care in a global world. A duality of priorities and challenges. Spine (Phila Pa 1976) 31(14):1515–1519. Google Scholar
  57. 57.
    Vo NV, Hartman RA, Patil PR, Risbud MV, Kletsas D, Iatridis JC, Hoyland JA, Le Maitre CL, Sowa GA, Kang JD (2016) Molecular mechanisms of biological aging in intervertebral discs. J Orthop Res 34(8):1289–1306. Google Scholar
  58. 58.
    Gopal D, Ho AL, Shah A, Chi JH (2012) Molecular basis of intervertebral disc degeneration. Adv Exp Med Biol 760:114–133Google Scholar
  59. 59.
    Jin L, Feng G, Reames DL, Shimer AL, Shen FH, Li X (2013) The effects of simulated microgravity on intervertebral disc degeneration. Spine J 13(3):235–242. Google Scholar
  60. 60.
    Bergknut N, Smolders LA, Grinwis GC, Hagman R, Lagerstedt AS, Hazewinkel HA, Tryfonidou MA, Meij BP (2013) Intervertebral disc degeneration in the dog. Part 1: anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration. Vet J 195(3):282–291. Google Scholar
  61. 61.
    Maatta JH, Kraatari M, Wolber L, Niinimaki J, Wadge S, Karppinen J, Williams FM (2014) Vertebral endplate change as a feature of intervertebral disc degeneration: a heritability study. Eur Spine J 23(9):1856–1862. Google Scholar
  62. 62.
    Li Y, Samartzis D, Campbell DD, Cherny SS, Cheung KM, Luk KD, Karppinen J, Song Y, Cheah KS, Chan D, Sham PC (2016) Two subtypes of intervertebral disc degeneration distinguished by large-scale population-based study. Spine J 16(9):1079–1089. Google Scholar
  63. 63.
    Gologorsky Y, Chi J (2014) Genetic predisposition to lumbar disc degeneration. Neurosurgery 74(2):N10–N11. Google Scholar
  64. 64.
    Gawri R, Rosenzweig DH, Krock E, Ouellet JA, Stone LS, Quinn TM, Haglund L (2014) High mechanical strain of primary intervertebral disc cells promotes secretion of inflammatory factors associated with disc degeneration and pain. Arthritis Res Ther 16(1):R21. Google Scholar
  65. 65.
    Peng Y, Lv FJ (2015) Symptomatic versus asymptomatic intervertebral disc degeneration: is inflammation the key? Crit Rev Eukaryot Gene Expr 25(1):13–21Google Scholar
  66. 66.
    Teixeira GQ, Pereira CL, Ferreira JR, Maia AF, Gomez-Lazaro M, Barbosa MA, Neidlinger-Wilke C, Goncalves RM (2017) Immunomodulation of human mesenchymal stem/stromal cells in intervertebral disc degeneration: insights from a proinflammatory/degenerative ex vivo model. Spine (Phila Pa 1976).
  67. 67.
    Pereira CL, Teixeira GQ, Ribeiro-Machado C, Caldeira J, Costa M, Figueiredo F, Fernandes R, Aguiar P, Grad S, Barbosa MA, Goncalves RM (2016) Mesenchymal stem/stromal cells seeded on cartilaginous endplates promote intervertebral disc regeneration through extracellular matrix remodeling. Sci Rep 6:33836. Google Scholar
  68. 68.
    Wang SZ, Rui YF, Lu J, Wang C (2014) Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies. Cell Prolif 47(5):381–390. Google Scholar
  69. 69.
    Ho G, Leung VY, Cheung KM, Chan D (2008) Effect of severity of intervertebral disc injury on mesenchymal stem cell-based regeneration. Connect Tissue Res 49(1):15–21. Google Scholar
  70. 70.
    Paesold G, Nerlich AG, Boos N (2007) Biological treatment strategies for disc degeneration: potentials and shortcomings. Eur Spine J 16(4):447–468. Google Scholar
  71. 71.
    Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, Berven S (2004) Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 32(3):430–434Google Scholar
  72. 72.
    Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K, Nakai T, Ando K, Hotta T (2003) Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 24(20):3531–3541Google Scholar
  73. 73.
    Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T (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(21):2379–2387Google Scholar
  74. 74.
    Chen S, Zhao L, Deng X, Shi D, Wu F, Liang H, Huang D, Shao Z (2017) Mesenchymal stem cells protect nucleus pulposus cells from compression-induced apoptosis by inhibiting the mitochondrial pathway. Stem Cells Int 2017:9843120. Google Scholar
  75. 75.
    Pecina M, Vukicevic S (2007) Biological aspects of bone, cartilage and tendon regeneration. Int Orthop 31(6):719–720. Google Scholar
  76. 76.
    Lind M, Bunger C (2005) Orthopaedic applications of gene therapy. Int Orthop 29(4):205–209. Google Scholar

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© SICOT aisbl 2018

Authors and Affiliations

  1. 1.Department of OrthopaedicsRWTH Aachen University ClinicAachenGermany
  2. 2.Department of Spine SurgeryEifelklinik St. BrigidaSimmerathGermany

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