RESEARCH STATUS ON MOLECULAR BASIS OF INTERVERTEBRAL DISC DEGENERATION AND REPAIRING EFFECT OF PLATELET-RICH PLASMA_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

GUIKeke ¹ ,  YUYonglin ²

1. Department of Orthopaedics, Jinshan Hospital, Fudan University, Shanghai, 201508, P. R. China;
2. Department of Orthopaedics, Huashan Hospital, Fudan University;

Corresponding author：

YUYonglin, Email: yuyonglin@fudan.edu.cn

Keywords：

Intervertebral disc degeneration; Platelet-rich plasma; Tissue repair; Biological therapy

DOI：

10.7507/1002-1892.20150025

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the research status on the molecular basis of intervertebral disc degeneration and the repairing effect of platelet-rich plasma. Methods The related literature about the molecular basis of intervertebral disc degeneration and the repairing effect of platelet-rich plasma was reviewed, analyzed, and summarized. Results The molecular basis of intervertebral disc degeneration includes genetic influences, cell senescence, decreased matrix production, increased degradative enzyme production, proinflammatory cytokine expression, apoptosis, and neural ingrowth. Platelet-rich plasma can release a series of growth factors to promote intervertebral disc cells proliferation, differentiation, and extracellular matrix synthesis. It can also inhibit proinflammatory effect and apoptosis. Conclusion Although the prospect of using platelet-rich plasma to repair intervertebral disc degeneration is encouraging, further studies are still needed.

Citation： GUIKeke, YUYonglin. RESEARCH STATUS ON MOLECULAR BASIS OF INTERVERTEBRAL DISC DEGENERATION AND REPAIRING EFFECT OF PLATELET-RICH PLASMA. Chinese Journal of Reparative and Reconstructive Surgery, 2015, 29(1): 123-128. doi: 10.7507/1002-1892.20150025 Copy

1.	Hughes SP, Freemont AJ, Hukins DW, et al. The pathogenesis of degeneration of the intervertebral disc and emerging therapies in the management of back pain. J Bone Joint Surg (Br), 2012, 94(10):1298-1304.
2.	Kepler CK, Anderson DG, Tannoury C, et al. Intervertebral disk degeneration and emerging biologic treatments. J Am Acad Orthop Surg, 2011, 19(9):543-553.
3.	Maidhof R, Alipui DO, Rafiuddin A, et al. Emerging trends in biological therapy for intervertebral disc degeneration. Discov Med, 2012, 14(79):401-411.
4.	Saucedo JM, Yaffe MA, Berschback JC, et al. Platelet-rich plasma. J Hand Surg Am, 2012, 37(3):587-589.
5.	Alsousou J, Ali A, Willett K, et al. The role of platelet-rich plasma in tissue regeneration. Platelets, 2013, 24(3):173-182.
6.	Podd D. Platelet-rich plasma therapy:origins and applications investigated. JAAPA, 2012, 25(6):44-49.
7.	Kepler CK, Ponnappan RK, Tannoury CA, et al. The molecular basis of intervertebral disc degeneration. Spine J, 2013, 13(3):318-330.
8.	Kim KW, Chung HN, Ha KY, et al. Senescence mechanisms of nucleus pulposus chondrocytes in human intervertebral discs. Spine J, 2009, 9(8):658-666.
9.	Le Maitre CL, Freemont AJ, Hoyland JA. Accelerated cellular senescence in degenerative intervertebral discs:a possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther, 2007, 9(3):R45.
10.	Duance VC, Crean JK, Sims TJ, et al. Changes in collagen crosslinking in degenerative disc disease and scoliosis. Spine, 1998, 23(23):2545-2551.
11.	Cs-Szabo G, Ragasa-San Juan D, Turumella V, et al. Changes in mRNA and protein levels of proteoglycans of the anulus fibrosus and nucleus pulposus during intervertebral disc degeneration. Spine, 2002, 27(20):2212-2219.
12.	Weiler C, Nerlich AG, Zipperer J, et al. 2002 SSE award competition in basic science:expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption. Eur Spine J, 2002, 11(4):308-320.
13.	Roberts S, Caterson B, Menage J, et al. Matrix metalloproteinases and aggrecanase:their role in disorders of the human intervertebral disc. Spine, 2000, 25(23):3005-3013.
14.	Gruber HE, Ingram JA, Hanley EN Jr. Immunolocalization of MMP-19 in the human intervertebral disc:implications for disc aging and degeneration. Biotech Histochem, 2005, 80(3-4):157-162.
15.	Pockert AJ, Richardson SM, Le Maitre CL, et al. Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases.
16.	during human intervertebral disc degeneration. Arthritis Rheum, 2009, 60(2):482-491.
17.	Le Maitre CL, Freemont AJ, Hoyland JA. Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J Pathol, 2004, 204(1):47-54.
18.	Le Maitre CL, Freemont AJ, Hoyland JA. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther, 2005, 7(4):R732-745.
19.	Jimbo K, Park JS, Yokosuka K, et al. Positive feedback loop of interleukin-1beta upregulating production of inflammatory mediators in human intervertebral disc cells in vitro. J Neurosurg Spine, 2005, 2(5):589-595.
20.	Cui LY, Liu SL, Ding Y, et al. IL-1beta sensitizes rat intervertebral disc cells to fas ligand mediated apoptosis in vitro. Acta Pharmacol Sin, 2007, 28(10):1671-1676.
21.	Freemont AJ. The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology (Oxford), 2009, 48(1):5-10.
22.	Igarashi T, Kikuchi S, Shubayev V, et al. 2000 Volvo Award winner in basic science studies:Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats. Spine, 2000, 25(23):2975-2980.
23.	Lee S, Moon CS, Sul D, et al. Comparison of growth factor and cytokine expression in patients with degenerated disc disease and herniated nucleus pulposus. Clin Biochem, 2009, 42(15):1504-1511.
24.	Hengartner MO. The biochemistry of apoptosis. Nature, 2000, 407(6805):770-776.
25.	Freemont AJ, Peacock TE, Goupille P, et al. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet, 1997, 350(9072):178-181.
26.	Johnson WE, Caterson B, Eisenstein SM, et al. Human intervertebral disc aggrecan inhibits nerve growth in vitro. Arthritis Rheum, 2002, 46(10):2658-2664.
27.	Johnson WE, Caterson B, Eisenstein SM, et al. Human intervertebral disc aggrecan inhibits endothelial cell adhesion and cell migration in vitro. Spine, 2005, 30(10):1139-1147.
28.	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):286-292.
29.	Gruber HE, Ingram JA, Hoelscher G, et al. Brain-derived neurotrophic factor and its receptor in the human and the sand rat intervertebral disc. Arthritis Res Ther, 2008, 10(4):R82.
30.	Alsousou J, Thompson M, Hulley P, et al. The biology of plateletrich plasma and its application in trauma and orthopaedic surgery:A review of the literature. J Bone Joint Surg Br, 2009, 91(8):987-996.
31.	Gentile P, Cervelli V. Autologous platelet-rich plasma:Guidelines in plastic surgery. Plast Reconstr Surg, 2010, 126(5):269e-270e.
32.	Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost, 2011, 105 Suppl 1:S13-33.
33.	Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma:implications for wound healing. Plast Reconstr Surg, 2004, 114(6):1502-1508.
34.	Kon E, Buda R, Filardo G, et al. Platelet-rich plasma:intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc, 2010, 18(4):472-479.
35.	Wang HL, Avila G. Platelet rich plasma:myth or reality? Eur J Dent, 2007, 1(4):192-194.
36.	Mishra A, Woodhall J Jr, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med, 2009, 28(1):113-125.
37.	Thompson JP, Oegema TR Jr, Bradford DS. Stimulation of mature canine intervertebral disc by growth factors. Spine, 1991, 16(3):253-260.
38.	Osada R, Ohshima H, Ishihara H, et al. 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, 1996, 14(5):690-699.
39.	Gruber HE, Fisher EC Jr, Desai B, et al. Human intervertebral disc cells from the annulus:three-dimensional culture in agarose or alginate and responsiveness to TGF-beta1. Exp Cell Res, 1997, 235(1):13-21.
40.	Gruber HE, Norton HJ, Hanley EN Jr. Anti-apoptotic effects of IGF- 1 and PDGF on human intervertebral disc cells in vitro. Spine, 2000, 25(17):2153-2157.
41.	Pratsinis H, Kletsas D. 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, 2007, 16(11):1858-1866.
42.	Hayes AJ, Ralphs JR. The response of foetal annulus fibrosus cells to growth factors:modulation of matrix synthesis by TGF-β₁ and IGF-1. Histochem Cell Biol, 2011, 136(2):163-175.
43.	Fujita N, Imai J, Suzuki T, et al. Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc. Biochem Biophys Res Commun, 2008, 372(2):367-372.
44.	Liu Y, Kong J, Chen BH, et al. 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), 2010, 123(15):2082-2087.
45.	Wang SZ, Rui YF, Tan Q, et al. Enhancing intervertebral disc repair and regeneration through biology:platelet-rich plasma as an alternative strategy. Arthritis Res Ther, 2013, 15(5):220.
46.	Akeda K, An HS, Pichika R, et al. Platelet-rich plasma (PRP) stimulates the extracellular matrix metabolism of porcine nucleus pulposus and anulus fibrosus cells cultured in alginate beads. Spine, 2006, 31(9):959-966.
47.	Chen WH, Lo WC, Lee JJ, et al. Tissue-engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF-beta1 in plateletrich plasma. J Cell Physiol, 2006, 209(3):744-754.
48.	Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng, 2007, 13(1):147-158.
49.	Sawamura K, Ikeda T, Nagae M, et al. Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs. Tissue Eng, 2009, 15(12):3719-3727.
50.	Gullung GB, Woodall JW, Tucci MA, et al. Platelet-rich plasma effects on degenerative disc disease:analysis of histology and imaging in an animal model. Evid Based Spine Care J, 2011, 2(4):13-18.
51.	Obata S, Akeda K, Imanishi T, et al. Effect of autologous plateletrich plasma-releasate on intervertebral disc degeneration in the rabbit anular puncture model:a preclinical study. Arthritis Res Ther, 2012, 14(6):R241.
52.	胡新锋, 王宸, 芮云峰. 自体富血小板血浆干预兔早期椎间盘退变的初步研究. 中国修复重建外科杂志, 2012, 26(8):978-984.
53.	Kim HJ, Yeom JS, Koh YG, et al. Anti-inflammatory effect of platelet-rich plasma on nucleus pulposus cells with response of TNF-α and IL-1. J Orthop Res, 2014, 32(4):551-556.
54.	Chen WH, Liu HY, Lo WC, et al. Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and plateletrich plasma. Biomaterials, 2009, 30(29):5523-5533.
55.	孟繁星, 李放, 叶超群, 等. 脂肪间充质干细胞复合血小板凝胶修复兔椎间盘退变. 中国组织工程研究, 2013, 17(21):3801-3808.
56.	Mietsch A, Neidlinger-Wilke C, Schrezenmeier H, et al. Evaluation of platelet-rich plasma and hydrostatic pressure regarding cell differentiation in nucleus pulposus tissue engineering. J Tissue Eng Regen Med, 2013, 7(3):244-252.
57.	谢雪涛, 张长青. 富血小板血浆在脊柱外科的应用. 国际骨科学杂志, 2011, 32(5):293-295.

1. Hughes SP, Freemont AJ, Hukins DW, et al. The pathogenesis of degeneration of the intervertebral disc and emerging therapies in the management of back pain. J Bone Joint Surg (Br), 2012, 94(10):1298-1304.
2. Kepler CK, Anderson DG, Tannoury C, et al. Intervertebral disk degeneration and emerging biologic treatments. J Am Acad Orthop Surg, 2011, 19(9):543-553.
3. Maidhof R, Alipui DO, Rafiuddin A, et al. Emerging trends in biological therapy for intervertebral disc degeneration. Discov Med, 2012, 14(79):401-411.
4. Saucedo JM, Yaffe MA, Berschback JC, et al. Platelet-rich plasma. J Hand Surg Am, 2012, 37(3):587-589.
5. Alsousou J, Ali A, Willett K, et al. The role of platelet-rich plasma in tissue regeneration. Platelets, 2013, 24(3):173-182.
6. Podd D. Platelet-rich plasma therapy:origins and applications investigated. JAAPA, 2012, 25(6):44-49.
7. Kepler CK, Ponnappan RK, Tannoury CA, et al. The molecular basis of intervertebral disc degeneration. Spine J, 2013, 13(3):318-330.
8. Kim KW, Chung HN, Ha KY, et al. Senescence mechanisms of nucleus pulposus chondrocytes in human intervertebral discs. Spine J, 2009, 9(8):658-666.
9. Le Maitre CL, Freemont AJ, Hoyland JA. Accelerated cellular senescence in degenerative intervertebral discs:a possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther, 2007, 9(3):R45.
10. Duance VC, Crean JK, Sims TJ, et al. Changes in collagen crosslinking in degenerative disc disease and scoliosis. Spine, 1998, 23(23):2545-2551.
11. Cs-Szabo G, Ragasa-San Juan D, Turumella V, et al. Changes in mRNA and protein levels of proteoglycans of the anulus fibrosus and nucleus pulposus during intervertebral disc degeneration. Spine, 2002, 27(20):2212-2219.
12. Weiler C, Nerlich AG, Zipperer J, et al. 2002 SSE award competition in basic science:expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption. Eur Spine J, 2002, 11(4):308-320.
13. Roberts S, Caterson B, Menage J, et al. Matrix metalloproteinases and aggrecanase:their role in disorders of the human intervertebral disc. Spine, 2000, 25(23):3005-3013.
14. Gruber HE, Ingram JA, Hanley EN Jr. Immunolocalization of MMP-19 in the human intervertebral disc:implications for disc aging and degeneration. Biotech Histochem, 2005, 80(3-4):157-162.
15. Pockert AJ, Richardson SM, Le Maitre CL, et al. Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases.
16. during human intervertebral disc degeneration. Arthritis Rheum, 2009, 60(2):482-491.
17. Le Maitre CL, Freemont AJ, Hoyland JA. Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J Pathol, 2004, 204(1):47-54.
18. Le Maitre CL, Freemont AJ, Hoyland JA. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther, 2005, 7(4):R732-745.
19. Jimbo K, Park JS, Yokosuka K, et al. Positive feedback loop of interleukin-1beta upregulating production of inflammatory mediators in human intervertebral disc cells in vitro. J Neurosurg Spine, 2005, 2(5):589-595.
20. Cui LY, Liu SL, Ding Y, et al. IL-1beta sensitizes rat intervertebral disc cells to fas ligand mediated apoptosis in vitro. Acta Pharmacol Sin, 2007, 28(10):1671-1676.
21. Freemont AJ. The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology (Oxford), 2009, 48(1):5-10.
22. Igarashi T, Kikuchi S, Shubayev V, et al. 2000 Volvo Award winner in basic science studies:Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats. Spine, 2000, 25(23):2975-2980.
23. Lee S, Moon CS, Sul D, et al. Comparison of growth factor and cytokine expression in patients with degenerated disc disease and herniated nucleus pulposus. Clin Biochem, 2009, 42(15):1504-1511.
24. Hengartner MO. The biochemistry of apoptosis. Nature, 2000, 407(6805):770-776.
25. Freemont AJ, Peacock TE, Goupille P, et al. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet, 1997, 350(9072):178-181.
26. Johnson WE, Caterson B, Eisenstein SM, et al. Human intervertebral disc aggrecan inhibits nerve growth in vitro. Arthritis Rheum, 2002, 46(10):2658-2664.
27. Johnson WE, Caterson B, Eisenstein SM, et al. Human intervertebral disc aggrecan inhibits endothelial cell adhesion and cell migration in vitro. Spine, 2005, 30(10):1139-1147.
28. 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):286-292.
29. Gruber HE, Ingram JA, Hoelscher G, et al. Brain-derived neurotrophic factor and its receptor in the human and the sand rat intervertebral disc. Arthritis Res Ther, 2008, 10(4):R82.
30. Alsousou J, Thompson M, Hulley P, et al. The biology of plateletrich plasma and its application in trauma and orthopaedic surgery:A review of the literature. J Bone Joint Surg Br, 2009, 91(8):987-996.
31. Gentile P, Cervelli V. Autologous platelet-rich plasma:Guidelines in plastic surgery. Plast Reconstr Surg, 2010, 126(5):269e-270e.
32. Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost, 2011, 105 Suppl 1:S13-33.
33. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma:implications for wound healing. Plast Reconstr Surg, 2004, 114(6):1502-1508.
34. Kon E, Buda R, Filardo G, et al. Platelet-rich plasma:intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc, 2010, 18(4):472-479.
35. Wang HL, Avila G. Platelet rich plasma:myth or reality? Eur J Dent, 2007, 1(4):192-194.
36. Mishra A, Woodhall J Jr, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med, 2009, 28(1):113-125.
37. Thompson JP, Oegema TR Jr, Bradford DS. Stimulation of mature canine intervertebral disc by growth factors. Spine, 1991, 16(3):253-260.
38. Osada R, Ohshima H, Ishihara H, et al. 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, 1996, 14(5):690-699.
39. Gruber HE, Fisher EC Jr, Desai B, et al. Human intervertebral disc cells from the annulus:three-dimensional culture in agarose or alginate and responsiveness to TGF-beta1. Exp Cell Res, 1997, 235(1):13-21.
40. Gruber HE, Norton HJ, Hanley EN Jr. Anti-apoptotic effects of IGF- 1 and PDGF on human intervertebral disc cells in vitro. Spine, 2000, 25(17):2153-2157.
41. Pratsinis H, Kletsas D. 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, 2007, 16(11):1858-1866.
42. Hayes AJ, Ralphs JR. The response of foetal annulus fibrosus cells to growth factors:modulation of matrix synthesis by TGF-β₁ and IGF-1. Histochem Cell Biol, 2011, 136(2):163-175.
43. Fujita N, Imai J, Suzuki T, et al. Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc. Biochem Biophys Res Commun, 2008, 372(2):367-372.
44. Liu Y, Kong J, Chen BH, et al. 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), 2010, 123(15):2082-2087.
45. Wang SZ, Rui YF, Tan Q, et al. Enhancing intervertebral disc repair and regeneration through biology:platelet-rich plasma as an alternative strategy. Arthritis Res Ther, 2013, 15(5):220.
46. Akeda K, An HS, Pichika R, et al. Platelet-rich plasma (PRP) stimulates the extracellular matrix metabolism of porcine nucleus pulposus and anulus fibrosus cells cultured in alginate beads. Spine, 2006, 31(9):959-966.
47. Chen WH, Lo WC, Lee JJ, et al. Tissue-engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF-beta1 in plateletrich plasma. J Cell Physiol, 2006, 209(3):744-754.
48. Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng, 2007, 13(1):147-158.
49. Sawamura K, Ikeda T, Nagae M, et al. Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs. Tissue Eng, 2009, 15(12):3719-3727.
50. Gullung GB, Woodall JW, Tucci MA, et al. Platelet-rich plasma effects on degenerative disc disease:analysis of histology and imaging in an animal model. Evid Based Spine Care J, 2011, 2(4):13-18.
51. Obata S, Akeda K, Imanishi T, et al. Effect of autologous plateletrich plasma-releasate on intervertebral disc degeneration in the rabbit anular puncture model:a preclinical study. Arthritis Res Ther, 2012, 14(6):R241.
52. 胡新锋, 王宸, 芮云峰. 自体富血小板血浆干预兔早期椎间盘退变的初步研究. 中国修复重建外科杂志, 2012, 26(8):978-984.
53. Kim HJ, Yeom JS, Koh YG, et al. Anti-inflammatory effect of platelet-rich plasma on nucleus pulposus cells with response of TNF-α and IL-1. J Orthop Res, 2014, 32(4):551-556.
54. Chen WH, Liu HY, Lo WC, et al. Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and plateletrich plasma. Biomaterials, 2009, 30(29):5523-5533.
55. 孟繁星, 李放, 叶超群, 等. 脂肪间充质干细胞复合血小板凝胶修复兔椎间盘退变. 中国组织工程研究, 2013, 17(21):3801-3808.
56. Mietsch A, Neidlinger-Wilke C, Schrezenmeier H, et al. Evaluation of platelet-rich plasma and hydrostatic pressure regarding cell differentiation in nucleus pulposus tissue engineering. J Tissue Eng Regen Med, 2013, 7(3):244-252.
57. 谢雪涛, 张长青. 富血小板血浆在脊柱外科的应用. 国际骨科学杂志, 2011, 32(5):293-295.

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Chinese Journal of Reparative and Reconstructive Surgery

RESEARCH STATUS ON MOLECULAR BASIS OF INTERVERTEBRAL DISC DEGENERATION AND REPAIRING EFFECT OF PLATELET-RICH PLASMA

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