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Intradiscal Stem Cell Implantation for Degenerative Disk Disease

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Minimally Invasive Surgery in Orthopedics

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Abstract

Chronic lower back pain (CLBP) is a challenging socioeconomic health matter that leads to progressive debilitation, lost work days, and an extensive impact on the healthcare system. Treatment of CLBP has focused primarily on conservative treatments and interventional pain procedures. If those modalities fail, surgical removal of the pain generating anatomical structure is undertaken, and reconstruction of the spine is performed. These treatments include diskectomy, spinal arthrodesis, total disk replacement, and facet joint replacement. Many of these treatments have variable efficacy and often lead to adjacent spinal segment degeneration. The long-term outcome of these procedures is that a variable percentage of patients obtain enough relief such that they can return to the workforce, and often patients either do not obtain the relief required or have adjacent segment degeneration that results in further surgical reconstruction. The common theme to both nonoperative and operative management is that treatment is focused on a reaction to the disease process. Regenerative medicine however focuses on repair of the damaged spinal structures such that we alter the natural history of the disease process, thereby both reducing symptomatology as well as preventing future spinal degeneration. This chapter presents over 40 years of data that has led us to recent clinical trials examining the use of mesenchymal stem cells to regenerate the intervertebral disk. Current evidence suggests that the mesenchymal stem cell has the ability to both halt the natural history of disk degeneration, alleviate painful symptomatology, and potentially alter the occurrence of adjacent segment disease.

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References

  1. Luo X, Pietrobon R, Sun SX, Liu GG, Hey L. Estimates and patterns of direct health care expenditures among individuals with back pain in the United States. Spine. 2004;29(1):79–86.

    Article  PubMed  Google Scholar 

  2. Guo HR, Tanaka S, Halperin WE, Cameron LL. Back pain prevalence in US industry and estimates of lost workdays. Am J Public Health. 1999;89(7):1029–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dillane JB, Fry J, Kalton G. Acute back syndrome: a study from general practice. Br Med J. 1966;2:82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Spratt KF, Lehmann TR, Weinstein JN, et al. A new approach to low back physical examination. Behavioral assessment of mechanical signs. Spine. 1990;15(2):96–102.

    Article  CAS  PubMed  Google Scholar 

  5. Nachemson AL. The natural course of low back pain. In: White AA, editor. American Academy of orthopedic surgeons symposium on idiopathic low back pain. St Louis: CV Mosby; 1982. p. 46–51.

    Google Scholar 

  6. DePalma MJ, Ketchum JM, Trussell BS, Saullo TR, Slipman CW. Does the location of low back pain predict its source? PM R. 2011;3(1):33–9.

    Article  PubMed  Google Scholar 

  7. DePalma MJ, Ketchum JM, Saullo T. What is the source of chronic low back pain and does age play a role? Pain Med. 2011;12(2):224–33.

    Article  PubMed  Google Scholar 

  8. Bogduk NBL. Back pain and neck pain: an evidence-based update. Seattle: IASP Press; 1999.

    Google Scholar 

  9. Borenstein D. Does osteoarthritis of the lumbar spine cause chronic low back pain? Curr Pain Headache Rep. 2004;8:512–7.

    Article  PubMed  Google Scholar 

  10. Boswell MV, Shah RV, Everett CR, et al. Interventional techniques in the management of chronic spinal pain: evidence-based practice guidelines. Pain Physician. 2005;8:1–47.

    PubMed  Google Scholar 

  11. Dreyer SJ, Dreyfuss PH. Low back pain and zygapophysial (facet) joints. Arch Phys Med Rehabil 1996;77:290–300; Jackson RP. The facet syndrome: myth or reality? Clin Orthop 1992;279:110–21.

    Google Scholar 

  12. Ghormley RK. Low back pain with special reference to the articular facet, with presentation of operative procedure. JAMA. 1933;101:1773–7.

    Article  Google Scholar 

  13. Kuslich SD, Ulstrom CL, Michael CJ. The tissue origin of low back pain and sciatica: a report of pain response to tissue stimulation during operations on the lumbar spine using local anesthesia. Orthop Clin North Am. 1991;22:181–716.

    CAS  PubMed  Google Scholar 

  14. Manchikanti L, Singh V, Pampati V, et al. Evaluation of the relative contributions of various structures in chronic low back pain. Pain Physician. 2001;4:308–16.

    CAS  PubMed  Google Scholar 

  15. Marks RC, Houston T, Thulbourne T. Facet joint injection and facet nerve block: a randomized comparison in 86 patients with chronic low back pain. Pain. 1992;49:325–8.

    Article  CAS  PubMed  Google Scholar 

  16. Mooney V, Robertson J. The facet syndrome. Clin Orthop. 1976;115:149–56.

    PubMed  Google Scholar 

  17. Schwarzer AC, Aprill CN, Derby R, Fortin J, Kine G, Bogduk N. Clinical features of patients with pain stemming from the lumbar zygapophysial joints: is the lumbar facet syndrome a clinical entity? Spine. 1994;19:1132–7.

    Article  CAS  PubMed  Google Scholar 

  18. Schwarzer AC, Wang S, Bogduk N, McNaught PJ, Laurent R. Prevalence and clinical features of lumbar zygapophysial joint pain: a study in an Australian population with chronic low back pain. Ann Rheum Dis. 1995;54:100–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sehgal N, Shah RV, McKenzie-Brown A, Everett CR. Diagnostic utility of facet (zygapophysial) joint injections in chronic spinal pain: a systematic review of evidence. Pain Physician. 2005;8:211–24.

    PubMed  Google Scholar 

  20. Shealy CN. The role of the spinal facets in back and sciatic pain. Headache. 1974;14:101–4.

    Article  CAS  PubMed  Google Scholar 

  21. Schwarzer AC, Aprill CN, Derby R, et al. The prevalence and clinical features of internal disc disruption in patients with chronic low back pain. Spine. 1995;20(17):1878–81.

    Article  CAS  PubMed  Google Scholar 

  22. http://literature.drgoreonline.com/disc.pdf. 21 Nov 2015.

  23. Raj PP. Intervertebral disc: anatomy-physiology-pathophysiology-treatment. Pain Pract. 2008;8(1):18–44.

    Article  PubMed  Google Scholar 

  24. Johnson WE, Caterson B, Eisenstein SM, Hynds DL, Snow DM, Roberts S. Human intervertebral disc aggrecan inhibits nerve growth in vitro. Arthritis Rheum. 2002;46(10):2658–64.

    Article  CAS  PubMed  Google Scholar 

  25. MacLean JJ, Lee CR, Alini M, et al. The effects of short-term load duration on anabolic and catabolic gene expression in the rat tail intervertebral disc. J Orthop Res. 2005;23:1120–7.

    Article  CAS  PubMed  Google Scholar 

  26. Korecki C, et al. Intervertebral disc cell response to dynamic compression is age and frequency dependent. J Orthop Res. 2009;27(6):800–6.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Le Maitre CL, Freemont AJ, Hoyland JA. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther. 2007;9(3):R45.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Peng B, Wu W, Hou S, et al. The pathogenesis of discogenic low back pain. J Bone Joint Surg (Br). 2005;87-B:62–7.

    Google Scholar 

  29. Peng B, Hao J, Hou S, et al. Possible pathogenesis of painful intervertebral disc degeneration. Spine. 2006;31(5):560–6.

    Article  PubMed  Google Scholar 

  30. Kepler CK, et al. Intervertebral disk degeneration and emerging biological treatments. J Am Acad Orthop Surg. 2011;19(9):543–53.

    Article  PubMed  Google Scholar 

  31. Burke JG, Watson RWG, McCormack D, et al. Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. J Bone Joint Surg (Br). 2002;84-B:196–201.

    Article  Google Scholar 

  32. Weiler C, Nerlich AG, Bachmeier BE, et al. Expression and distribution of tumor necrosis factor alpha in human lumbar intervertebral discs: a study in surgical specimen and autopsy controls. Spine. 2004;30(1):44–54.

    Article  Google Scholar 

  33. Coppes MH, Marani E, Thomeer RWM, Groen GJ. Innervation of “painful” lumbar discs. Spine. 1997;22:2342–50.

    Article  CAS  PubMed  Google Scholar 

  34. Brown M, Hukkanen M, McCarthy I, et al. Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease. J Bone Joint Surg (Br). 1997;79-B:147–53.

    Article  Google Scholar 

  35. Freemont AJ, Peacock TE, Goupille P, Hoyland JA, O’Brien J, Jayson MI. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet. 1997;350(9072):178–81.

    Article  CAS  PubMed  Google Scholar 

  36. Freemont AJ, Watkins A, Le Maitre C, et al. Nerve growth factor expression and innervation of the painful intervertebral disc. J Pathol. 2002;197(3):286–92.

    Article  CAS  PubMed  Google Scholar 

  37. Cunha JM, Cunha FQ, Poole S, et al. Cytokine-mediated inflammatory hyperalgesia limited by interleukin-1 receptor antagonist. Br J Pharmacol. 2000;130:1418–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Handa T, Ishihara H, Ohshima H, et al. Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc. Spine. 1997;22:1085–91.

    Article  CAS  PubMed  Google Scholar 

  39. Ohshima H, Urban JP, Bergel DH. Effect of static load on matrix synthesis rates in the intervertebral disc measured in vitro by a new perfusion technique. J Orthop Res. 1995;13:22–9.

    Article  CAS  PubMed  Google Scholar 

  40. Adams MA, Freeman BJC, Morrison HP, et al. Mechanical initiation of intervertebral disc degeneration. Spine. 2000;25:1625–36.

    Article  CAS  PubMed  Google Scholar 

  41. Maroudas A, Stockwell RA, Nachemson A, et al. Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. J Anat. 1975;120:113–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Olmarker E, Blomquist J, Stromberg J, et al. Inflammatogenic properties of nucleus pulposus. Spine. 1995;20:665–9.

    Article  CAS  PubMed  Google Scholar 

  43. Gronblad M, Virri J, Ronkko S, et al. A controlled biochemical and immunohistochemical study of human synovial-type (group II) phospholipase a2 and inflammatory cells in macroscopically normal, degenerated, and herniated human intervertebral disc tissues. Spine. 1996;21:2531–8.

    Article  CAS  PubMed  Google Scholar 

  44. Nachemson A, Lewin T, Maroudas A, et al. In vitro diffusion of dye through the endplates and annulus fibrosus of human lumbar intervertebral discs. Acta Orthop Scand. 1970;41:589–607.

    Article  CAS  PubMed  Google Scholar 

  45. Moneta GB, Videman T, Kaivanto K, et al. Reported pain during lumbar discography as a function of annular ruptures and disc degeneration: a re-analysis of 833 discograms. Spine. 1994;19(17):1968–74.

    Article  CAS  PubMed  Google Scholar 

  46. Cohen SP, Raja SN. Pathogenesis, diagnosis, and treatment of lumbar zygapophysial (facet) joint pain. Anesthesiology. 2007;106(3):591–614. Review.

    Article  PubMed  Google Scholar 

  47. Wolfer LR, Derby R, Lee JE, et al. Systematic review of lumbar provocation discography in asymptomatic subjects with a metaanalysis of false-positive rates. Pain Physician. 2008;11:513–38.

    PubMed  Google Scholar 

  48. Walsh TR, Weinstein JN, Spratt KF, Lehmann TR, Aprill C, Sayre H. The question of discography revisited. A controlled prospective study of normal volunteers to determine the false positive rate. J Bone Joint Surg Am. 1990;72-A(7):1081–8.

    Google Scholar 

  49. DePalma MJ, Lee JE, Peterson L, Wolfer L, Ketchum J, Derby R. Are outer annular fissures stimulated during diskography the source of diskogenic low-back pain? An analysis of analgesic diskography data. Pain Med. 2009;10(3):488–94.

    Article  PubMed  Google Scholar 

  50. Carragee E, et al. 2009 ISSLS Prize Winner: does discography cause accelerated progression of degeneration changes in the lumbar disc: a ten-year matched cohort study. Spine (Phila Pa 1976). 2009;34(21):2338–45.

    Article  Google Scholar 

  51. An HS, Masuda K, Inoue N. Intervertebral disk degeneration: biological and biomechanical factors. J Orthop Sci. 2006;11(5):541–52.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Risbud MV, Shapiro I. Role of cytokines in intervertebral disc degeneration: pain and disc-content. Nat Rev Rheumatol. 2014;10(1):44–56.

    Article  CAS  PubMed  Google Scholar 

  53. Woods B, et al. Gene therapy for intervertebral disc degeneration. Orthop Clin North Am. 2011;42(4):563–74.

    Article  PubMed  Google Scholar 

  54. Bowles RD, et al. Tissue-engineered intervertebral discs produce new matrix, maintain disc height, and restore biomechanical function to the rodent spine. Proc Natl Acad Sci. 2011;108(32):13106–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Adkisson HD, et al. Immune evasion by neocartilage-derived chondrocytes: implications for biologic repair of joint articular cartilage. Stem Cell Res. 2010;4(1):57–68.

    Article  CAS  PubMed  Google Scholar 

  56. Song H, Kwon K, Lim S, et al. Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions. Mol Cells. 2005;19:402–7.

    CAS  PubMed  Google Scholar 

  57. Zhang YG, Guo X, Xu P, et al. Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans. Clin Orthop Relat Res. 2005;430:219–26.

    Article  PubMed  Google Scholar 

  58. Sakai D, Mochida J, Iwashina T, et al. Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine. 2005;30:2379–87.

    Article  PubMed  Google Scholar 

  59. Sakai D, Mochida J, Iwashina T, et al. Regenerative effects of transplanting mesenchymal stem cells embedded in collagen to the degenerated intervertebral disc. Biomaterials. 2006;27:335–45.

    Article  CAS  PubMed  Google Scholar 

  60. Sheikh H, Zakharian K, De La Torre RP, et al. In vivo intervertebral disc regeneration using stem cell-derived chondroprogenitors. J Neurosurg Spine. 2009;10:265–72.

    Article  PubMed  Google Scholar 

  61. Ghosh P, Shimmon S, Wu J, et al. STRO-3+ immunoselected allogeneic mesenchymal progenitor cells injected into degenerate intervertebral discs reconstitute the proteoglycans of the nucleus pulposus-an experimental study in sheep. Presented at: Annual Meeting of the Orthopaedic Research Society, Long Beach, 2011.

    Google Scholar 

  62. Siddiqi F, Hayes V, Graver A, Grande D. Stem cell-TGFb combination therapy for treatment of the degenerative intervertebral disc – can stem cells initiate a healing responce on their own. Podium Presentation NASS 2013.

    Google Scholar 

  63. Caplan AI. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol. 2007;213:341–7.

    Article  CAS  PubMed  Google Scholar 

  64. Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970;3:393–403.

    CAS  PubMed  Google Scholar 

  65. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997;276:71–4.

    Article  CAS  PubMed  Google Scholar 

  66. Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008;3:301–13.

    Article  CAS  PubMed  Google Scholar 

  67. Simmons PJ, Przepiorka D, Thomas ED, Torok-Storb B. Host origin of marrow stromal cells following allogeneic bone marrow transplantation. Nature. 1987;328:429–32.

    Article  CAS  PubMed  Google Scholar 

  68. Friedenstein AJ. Stromal mechanisms of bone marrow: cloning in vitro and retransplantation in vivo. Haematol Blood Transfus. 1980;25:19–29.

    CAS  PubMed  Google Scholar 

  69. Simmons PJ, Torok-Storb B. Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood. 1991;78:55–62.

    CAS  PubMed  Google Scholar 

  70. Gronthos S, Zannettino AC, Hay SJ, Shi S, Graves SE, Kortesidis A, Simmons PJ. Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J Cell Sci. 2003;116:1827–35.

    Article  CAS  PubMed  Google Scholar 

  71. Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, Tagliafico E, Ferrari S, Robey PG, Riminucci M, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell. 2007;131:324–36.

    Article  CAS  PubMed  Google Scholar 

  72. Van Vlasselaer P, Falla N, Snoeck H, Mathieu E. Characterization and purification of osteogenic cells from murine bone marrow by two-color cell sorting using anti-Sca-1 monoclonal antibody and wheat germ agglutinin. Blood. 1994;84:753–63.

    CAS  PubMed  Google Scholar 

  73. Prockop DJ. “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clin Pharmacol Ther. 2007;82:241–3.

    Article  CAS  PubMed  Google Scholar 

  74. Le Blanc K, Ringden O. Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005;11:321–34.

    Article  CAS  PubMed  Google Scholar 

  75. Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, Galun E, Rachmilewitz J. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood. 2005;105:2214–9.

    Article  CAS  PubMed  Google Scholar 

  76. Ganey T, Libera J, Moos V, Alasevic O, Fritsch KG, Meisel HJ, Hutton WC. Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine. 2003;28:2609–20.

    Article  PubMed  Google Scholar 

  77. Yoshikawa T, et al. Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine (Phila Pa 1976). 2010;35(11):E475–80.

    Article  Google Scholar 

  78. Hohaus C, et al. Cell transplantation in lumbar spine disc degeneration disease. Eur Spine J. 2008;17 Suppl 4:S492–503.

    Article  Google Scholar 

  79. Helgeson MD, Bevevino AJ, Hilibrand AS. Update on the evidence for adjacent segment degeneration and disease. Spine J. 2013. doi:10.1016/j.spinee.2012.12.009. pii: S1529-9430(13)00070-3.

    Google Scholar 

  80. http://www.mesoblast.com/clinical-trial-results/mpc-06-id-phase-2. 21 Nov 2015.

  81. Coric D, et al. Prospective study of disc repair with allogeneic chondrocytes presented at the 2012 Joint Spine Section Meeting. J Neurosurg Spine. 2013;18(1):85–95.

    Article  PubMed  Google Scholar 

  82. http://thejns.org/doi/pdf/10.3171/2012.10.SPINE12512. 21 Nov 2015.

  83. Bertagnoli R, et al. EuroDisc study – assessment of efficacy and safety of sequestrectomy plus autologous disc chondrocytes – second analysis of a subgroup. Spine J. 2007;7 Suppl 5:56S–7.

    Article  Google Scholar 

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Authors and Affiliations

  1. Trinity Spine Center – Trinity Stem Cell Institute, Odessa, FL, USA

    Farhan Siddiqi, Victor Hayes, Daniel Grande & Mohamad Hakim

Authors
  1. Farhan Siddiqi
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  2. Victor Hayes
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  3. Daniel Grande
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  4. Mohamad Hakim
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Correspondence to Farhan Siddiqi .

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Editors and Affiliations

  1. Orthopedic Service Line, Northwell Health , New York, New York, USA

    Giles R. Scuderi

  2. Department of Orthopedic Surgery, Rutgers-Robert Wood JohnsonMedicalSchool Department of Orthopedic Surgery, New Brunswick, New Jersey, USA

    Alfred J. Tria

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Siddiqi, F., Hayes, V., Grande, D., Hakim, M. (2016). Intradiscal Stem Cell Implantation for Degenerative Disk Disease. In: Scuderi, G., Tria, A. (eds) Minimally Invasive Surgery in Orthopedics. Springer, Cham. https://doi.org/10.1007/978-3-319-34109-5_111

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  • DOI: https://doi.org/10.1007/978-3-319-34109-5_111

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