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Growth factors and platelet-rich plasma: promising biological strategies for early intervertebral disc degeneration

International Orthopaedics volume 39, pages 927–934 (2015)Cite this article

Abstract

Intervertebral disc degeneration (IDD) is a complex process with the mechanism not fully elucidated. The current clinical treatments for IDD are mainly focused on providing symptomatic relief without addressing the underlying cause of the IDD. Biological therapeutic strategies to repair and regenerate the degenerated discs are drawing more attention. Growth factor therapy is one of the biological strategies and holds promising prospects. As a promising bioactive substance, platelet-rich plasma (PRP) is considered to be an ideal growth factor “cocktail” for intervertebral disc (IVD) restoration. Results from many in vitro and in vivo studies have confirmed the efficacy of growth factors and PRP in IVD repair and regeneration. It is essential to advance the research on growth factor therapy and associated mechanism for IDD. This article reviews the background of IDD, current concepts in growth factor and PRP-related therapy for IDD. Future research perspectives and clinical directions are also discussed.

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References

  1. McBeth J, Jones K (2007) Epidemiology of chronic musculoskeletal pain. Best Pract Res Clin Rheumatol 21:403–425

    Article  PubMed  Google Scholar 

  2. Cheng J, Wang H, Zheng W et al (2013) Reoperation after lumbar disc surgery in two hundred and seven patients. Int Orthop 37:1511–1517

    Article  PubMed Central  PubMed  Google Scholar 

  3. Wei J, Song Y, Sun L et al (2013) Comparison of artificial total disc replacement versus fusion for lumbar degenerative disc disease: a meta-analysis of randomized controlled trials. Int Orthop 37:1315–1325

    Article  PubMed Central  PubMed  Google Scholar 

  4. Chen Y, He Z, Yang H et al (2013) Clinical and radiological results of total disc replacement in the cervical spine with preoperative reducible kyphosis. Int Orthop 37:463–468

    Article  PubMed Central  PubMed  Google Scholar 

  5. Paesold G, Nerlich AG, Boos N (2007) Biological treatment strategies for disc degeneration: potentials and shortcomings. Eur Spine J 16:447–468

    Article  PubMed Central  PubMed  Google Scholar 

  6. Hu X, Wang C, Rui Y (2012) An experimental study on effect of autologous platelet-rich plasma on treatment of early intervertebral disc degeneration. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 26:977–983

    CAS  PubMed  Google Scholar 

  7. Wang SZ, Rui YF, Tan Q et al (2013) Enhancing intervertebral disc repair and regeneration through biology: platelet-rich plasma as an alternative strategy. Arthritis Res Ther 15:220

    Article  PubMed Central  PubMed  Google Scholar 

  8. Humzah MD, Soames RW (1988) Human intervertebral disc: structure and function. Anat Rec 220:337–356

    Article  CAS  PubMed  Google Scholar 

  9. Cassidy JJ, Hiltner A, Baer E (1989) Hierarchical structure of the intervertebral disc. Connect Tissue Res 23:75–88

    Article  CAS  PubMed  Google Scholar 

  10. Eyre DR, Muir H (1976) Types I and II collagens in intervertebral disc. Interchanging radial distributions in annulus fibrosus. Biochem J 157:267–270

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Roughley PJ (2006) The structure and function of cartilage proteoglycans. Eur Cell Mater 12:92–101

    CAS  PubMed  Google Scholar 

  12. Urban JP, Smith S, Fairbank JC (2004) Nutrition of the intervertebral disc. Spine 29:2700–2709

    Article  PubMed  Google Scholar 

  13. Hadjipavlou AG, Tzermiadianos MN, Bogduk N et al (2008) The pathophysiology of disc degeneration: a critical review. J Bone Joint Surg Br 90:1261–1270

    Article  CAS  PubMed  Google Scholar 

  14. Singh K, Masuda K, An HS (2005) Animal models for human disc degeneration. Spine J 5:267S–279S

    Article  PubMed  Google Scholar 

  15. Smith LJ, Nerurkar NL, Choi KS et al (2011) Degeneration and regeneration of the intervertebral disc: lessons from development. Dis Model Mech 4:31–41

    Article  PubMed Central  PubMed  Google Scholar 

  16. Walmsley R (1953) The development and growth of the intervertebral disc. Edinb Med J 60:341–364

    CAS  PubMed  Google Scholar 

  17. Hunter CJ, Matyas JR, Duncan NA (2003) The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. Tissue Eng 9:667–677

    Article  CAS  PubMed  Google Scholar 

  18. Choi KS, Cohn MJ, Harfe BD (2008) Identification of nucleus pulposus precursor cells and notochordal remnants in the mouse: implications for disk degeneration and chordoma formation. Dev Dyn 237:3953–3958

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Feng G, Yang X, Shang H et al (2010) Multipotential differentiation of human annulus fibrosus cells: an in vitro study. J Bone Joint Surg Am 92:675–685

    Article  PubMed  Google Scholar 

  20. Henriksson H, Thornemo M, Karlsson C et al (2009) Identification of cell proliferation zones, progenitor cells and a potential stem cell niche in the intervertebral disc region: a study in four species. Spine 34:2278–2287

    Article  PubMed  Google Scholar 

  21. Sakai D, Nakamura Y, Nakai T et al (2012) Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc. Nat Commun 3:1264

    Article  PubMed Central  PubMed  Google Scholar 

  22. Konttinen YT, Kemppinen P, Li TF et al (1999) Transforming and epidermal growth factors in degenerated intervertebral discs. J Bone Joint Surg Br 81:1058–1063

    Article  CAS  PubMed  Google Scholar 

  23. Jin H, Shen J, Wang B et al (2011) TGF-β signaling plays an essential role in the growth and maintenance of intervertebral disc tissue. FEBS Lett 585:1209–1215

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Tolonen J, Grönblad M, Vanharanta H et al (2006) Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor. Eur Spine J 15:588–596

    Article  PubMed Central  PubMed  Google Scholar 

  25. Le Maitre CL, Richardson SM, Baird P et al (2005) Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc. J Pathol 207:445–452

    Article  PubMed  Google Scholar 

  26. Wang H, Kroeber M, Hanke M et al (2004) Release of active and depot GDF-5 after adenovirus-mediated overexpression stimulates rabbit and human intervertebral disc cells. J Mol Med (Berl) 82:126–134

    Article  CAS  Google Scholar 

  27. Fujita N, Imai J, Suzuki T et al (2008) Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc. Biochem Biophys Res Commun 372:367–372

    Article  CAS  PubMed  Google Scholar 

  28. Marx RE (2001) Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent 10:225–228

    Article  CAS  PubMed  Google Scholar 

  29. Brass L (2010) Understanding and evaluating platelet function. Hematol Am Soc Hematol Educ Program 2010:387–396

    Article  Google Scholar 

  30. Bir SC, Esaki J, Marui A et al (2011) Therapeutic treatment with sustained-release platelet-rich plasma restores blood perfusion by augmenting ischemia-induced angiogenesis and arteriogenesis in diabetic mice. J Vasc Res 48:195–205

    Article  PubMed  Google Scholar 

  31. Yu J, Ustach C, Kim HR (2003) Platelet-derived growth factor signaling and human cancer. J Biochem Mol Biol 36:49–59

    Article  CAS  PubMed  Google Scholar 

  32. Antoniades HN, Williams LT (1983) Human platelet-derived growth factor: structure and function. Fed Proc 42:2630–2634

    CAS  PubMed  Google Scholar 

  33. Knighton DR, Hunt TK, Thakral KK et al (1982) Role of platelets and fibrin in the healing sequence: an in vivo study of angiogenesis and collagen synthesis. Ann Surg 196:379–388

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Hosgood G (1993) Wound healing. The role of platelet-derived growth factor and transforming growth factor beta. Vet Surg 22:490–495

    Article  CAS  PubMed  Google Scholar 

  35. Sánchez-González DJ, Méndez-Bolaina E, Trejo-Bahena NI (2012) Platelet-rich plasma peptides: key for regeneration. Int J Pept 2012:532519

    Article  PubMed Central  PubMed  Google Scholar 

  36. Brown GL, Nanney LB, Griffen J et al (1989) Enhancement of wound healing by topical treatment with epidermal growth factor. N Engl J Med 321:76–79

    Article  CAS  PubMed  Google Scholar 

  37. Spencer EM, Tokunaga A, Hunt TK (1993) Insulin-like growth factor binding protein-3 is present in the alpha-granules of platelets. Endocrinology 132:996–1001

    CAS  PubMed  Google Scholar 

  38. Karppinen J, Shen FH, Luk KD et al (2011) Management of degenerative disk disease and chronic low back pain. Orthop Clin North Am 42:513–528

    Article  PubMed  Google Scholar 

  39. Yoon ST, Patel NM (2006) Molecular therapy of the intervertebral disc. Eur Spine J 15:S379–S388

    Article  PubMed  Google Scholar 

  40. Kepler CK, Anderson DG, Tannoury C et al (2011) Intervertebral disk degeneration and emerging biologic treatments. J Am Acad Orthop Surg 19:543–553

    PubMed  Google Scholar 

  41. Nishida K, Suzuki T, Kakutani K et al (2008) Gene therapy approach for disc degeneration and associated spinal disorders. Eur Spine J 17:459–466

    Article  PubMed Central  PubMed  Google Scholar 

  42. Masuda K, An HS (2006) Prevention of disc degeneration with growth factors. Eur Spine J 15:S422–S432

    Article  PubMed  Google Scholar 

  43. Sakai D (2008) Future perspectives of cell-based therapy for intervertebral disc disease. Eur Spine J 17:452–458

    Article  PubMed Central  PubMed  Google Scholar 

  44. Sakai D, Mochida J, Iwashina T et al (2005) Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine 30:2379–2387

    Article  PubMed  Google Scholar 

  45. Zhang YG, Guo X, Xu P et al (2005) Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans. Clin Orthop Relat Res 430:219–226

    Article  PubMed  Google Scholar 

  46. Xie X, Wang Y, Zhao C et al (2012) Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials 33:7008–7018

    Article  CAS  PubMed  Google Scholar 

  47. Bowles RD, Gebhard HH, Härtl R et al (2011) Tissue-engineered intervertebral discs produce new matrix, maintain disc height, and restore biomechanical function to the rodent spine. Proc Natl Acad Sci U S A 108:13106–13111

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Wang SZ, Rui YF, Lu J et al (2014) Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies. Cell Prolif 47:381–390

    Article  CAS  PubMed  Google Scholar 

  49. Thompson JP, Oegema TR Jr, Bradford DS (1991) Stimulation of mature canine intervertebral disc by growth factors. Spine 16:253–260

    Article  CAS  PubMed  Google Scholar 

  50. Hayes AJ, Ralphs JR (2011) The response of foetal annulus fibrosus cells to growth factors: modulation of matrix synthesis by TGF-β1 and IGF-1. Histochem Cell Biol 136:163–175

    Article  CAS  PubMed  Google Scholar 

  51. Lee KI, Moon SH, Kim H et al (2012) Tissue engineering of the intervertebral disc with cultured nucleus pulposus cells using atelocollagen scaffold and growth factors. Spine 37:452–458

    Article  PubMed  Google Scholar 

  52. Gilbertson L, Ahn SH, Teng PN et al (2008) The effects of recombinant human bone morphogenetic protein-2, recombinant human bone morphogenetic protein-12, and adenoviral bone morphogenetic protein-12 on matrix synthesis in human annulus fibrosis and nucleus pulposus cells. Spine J 8:449–456

    Article  PubMed  Google Scholar 

  53. Kim DJ, Moon SH, Kim H et al (2003) Bone morphogenetic protein-2 facilitates expression of chondrogenic, not osteogenic, phenotype of human intervertebral disc cells. Spine 28:2679–2684

    Article  PubMed  Google Scholar 

  54. Masuda K, Takegami K, An H et al (2003) Recombinant osteogenic protein-1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads. J Orthop Res 21:922–930

    Article  CAS  PubMed  Google Scholar 

  55. Takegami K, An HS, Kumano F et al (2005) Osteogenic protein-1 is most effective in stimulating nucleus pulposus and annulus fibrosus cells to repair their matrix after chondroitinase ABC-induced in vitro chemonucleolysis. Spine J 5:231–238

    Article  PubMed  Google Scholar 

  56. Imai Y, Miyamoto K, An HS et al (2007) Recombinant human osteogenic protein-1 upregulates proteoglycan metabolism of human annulus fibrosus and nucleus pulposus cells. Spine 32:1303–1309

  57. Li X, Leo BM, Beck G et al (2004) Collagen and proteoglycan abnormalities in the GDF-5-deficient mice and molecular changes when treating disk cells with recombinant growth factor. Spine 29:2229–2234

  58. Chujo T, An HS, Akeda K et al (2006) Effects of growth differentiation factor-5 on the intervertebral disc–in vitro bovine study and in vivo rabbit disc degeneration model study. Spine 31:2909–2917

    Article  PubMed  Google Scholar 

  59. Gruber HE, Norton HJ, Hanley EN Jr (2000) Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro. Spine 25:2153–2157

    Article  CAS  PubMed  Google Scholar 

  60. Osada R, Ohshima H, Ishihara H et al (1996) Autocrine/paracrine mechanism of insulin-like growth factor-1 secretion, and the effect of insulin-like growth factor-1 on proteoglycan synthesis in bovine intervertebral discs. J Orthop Res 14:690–699

    Article  CAS  PubMed  Google Scholar 

  61. Pratsinis H, Kletsas D (2007) PDGF, bFGF and IGF-I stimulate the proliferation of intervertebral disc cells in vitro via the activation of the ERK and Akt signaling pathways. Eur Spine J 16:1858–1866

    Article  PubMed Central  PubMed  Google Scholar 

  62. Liu Y, Kong J, Chen BH, Hu YG (2010) Combined expression of CTGF and tissue inhibitor of metalloprotease-1 promotes synthesis of proteoglycan and collagen type II in rhesus monkey lumbar intervertebral disc cells in vitro. Chin Med J (Engl) 123:2082–2087

    CAS  Google Scholar 

  63. Krüger JP, Freymannx U, Vetterlein S et al (2013) Bioactive factors in platelet-rich plasma obtained by apheresis.Transfus Med Hemother 40(6):432–440

    Article  PubMed Central  PubMed  Google Scholar 

  64. Chen WH, Lo WC, Lee JJ et al (2006) Tissue-engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF-beta1 in platelet-rich plasma. J Cell Physiol 209:744–754

    Article  CAS  PubMed  Google Scholar 

  65. Chen WH, Liu HY, Lo WC et al (2009) Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biomaterials 30:5523–5533

    Article  CAS  PubMed  Google Scholar 

  66. Akeda K, An HS, Pichika R et al (2006) Platelet-rich plasma (PRP) stimulates the extracellular matrix metabolism of porcine nucleus pulposus and annulus fibrosus cells cultured in alginate beads. Spine 31:959–966

    Article  PubMed  Google Scholar 

  67. Pirvu TN, Schroeder JE, Peroglio M et al (2014) Platelet-rich plasma induces annulus fibrosus cell proliferation and matrix production. Eur Spine J 23:745–753

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Walsh AJ, Bradford DS, Lotz JC (2004) In vivo growth factor treatment of degenerated intervertebral discs. Spine 29:156–163

    Article  PubMed  Google Scholar 

  69. Kawakami M, Matsumoto T, Hashizume H et al (2005) Osteogenic protein-1 (osteogenic protein-1/bone morphogenetic protein-7) inhibits degeneration and pain-related behavior induced by chronically compressed nucleus pulposus in the rat. Spine 30:1933–1939

    Article  PubMed  Google Scholar 

  70. Nagae M, Ikeda T, Mikami Y et al (2007) Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng 13:147–158

    Article  CAS  PubMed  Google Scholar 

  71. Sawamura K, Ikeda T, Nagae M et al (2009) Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs. Tissue Eng Part A 15:3719–3727

    Article  CAS  PubMed  Google Scholar 

  72. Gullung GB, Woodall JW, Tucci MA et al (2011) Platelet-rich plasma effects on degenerative disc disease: analysis of histology and imaging in an animal model. Evid Based Spine Care J 2:13–18

    Article  PubMed Central  PubMed  Google Scholar 

  73. Obata S, Akeda K, Imanishi T et al (2012) Effect of autologous platelet-rich plasma-releasate on intervertebral disc degeneration in the rabbit annular puncture model: a preclinical study. Arthritis Res Ther 14:R241

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Lotz JC, Haughton V, Boden SD et al (2012) New treatments and imaging strategies in degenerative disease of the intervertebral disks. Radiology 264:6–19

    Article  PubMed  Google Scholar 

  75. Masuda K (2008) Biological repair of the degenerated intervertebral disc by the injection of growth factors. Eur Spine J 17:441–451

    Article  PubMed Central  PubMed  Google Scholar 

  76. Than KD, Rahman SU, Vanaman MJ et al (2012) Bone morphogenetic proteins and degenerative disk disease. Neurosurgery 70:996–1002

    Article  PubMed  Google Scholar 

  77. Fischer J, Kolk A, Wolfart S et al (2011) Future of local bone regeneration - protein versus gene therapy. J Craniomaxillofac Surg 39:54–64

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by Jiangsu Province Science Foundation of China (Grant No: BK20131304).

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The authors declare that they have no conflict of interest.

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    Affiliations

    1. Department of Orthopaedics, Zhongda Hospital, Medical School of Southeast University, 87 Ding Jia Qiao Road, Nanjing, Jiangsu, 210009, People’s Republic of China

      Shan-zheng Wang, Qing Chang, Jun Lu & Chen Wang

    2. Surgical Research Center, Medical School of Southeast University, 87 Ding Jia Qiao Road, Nanjing, Jiangsu, 210009, People’s Republic of China

      Chen Wang

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    1. Shan-zheng Wang
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    2. Qing Chang
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    Correspondence to Chen Wang.

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    Shan-zheng Wang and Qing Chang have contributed equally to this work.

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    Wang, Sz., Chang, Q., Lu, J. et al. Growth factors and platelet-rich plasma: promising biological strategies for early intervertebral disc degeneration. International Orthopaedics (SICOT) 39, 927–934 (2015). https://doi.org/10.1007/s00264-014-2664-8

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    Keywords

    • Intervertebral disc degeneration
    • Biological strategies
    • Growth factors
    • Platelet-rich plasma