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MUSCULOSKELETAL SURGERY

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01-08-2017 | Review

What is the clinical evidence on regenerative medicine in intervertebral disc degeneration?

Authors: M. Basso, L. Cavagnaro, A. Zanirato, S. Divano, C. Formica, M. Formica, L. Felli

Published in: MUSCULOSKELETAL SURGERY | Issue 2/2017

Abstract

Purpose

This review aims to explore and summarize the current clinical evidence about the use of regenerative medicine such as mesenchymal stem cells or platelet-rich plasma in intervertebral disc regeneration, in order to clarify the state of art of these novel approaches.

Materials and methods

We performed a research of the available literature about regenerative medicine strategies aiming to prevent intervertebral disc degeneration. All preclinical trials and in vitro studies were excluded. Only clinical trials were critically analysed.

Results

The manuscript selection produced a total of 7 articles concerning the use of regenerative therapies in intervertebral disc degeneration, covering the period between 2010 and 2016. Articles selected were 4 about the injection of mesenchymal stem cells-related results and 3 using platelet-rich plasma. The total population of patients treated with regenerative medicine strategies were 104 patients.

Conclusions

Regenerative medicine, such as the use of mesenchymal stem cells or platelet-rich plasma, in intradiscal disc degeneration has shown preclinical and clinical positive results. Randomized clinical trials studying the potential of MSCs intradiscal injection have not been conducted, and PRP effect has been studied only preliminarily. Additional more powered high-quality studies are needed to really appreciate the long-term safety and efficacy of regenerative medicine approaches in IDD.

de Schepper EI, Damen J, van Meurs JB, Ginai AZ, Popham M, Hofman A, Koes BW, Bierma-Zeinstra SM (2010) The association between lumbar disc degeneration and low back pain: the influence of age, gender, and individual radiographic features. Spine 35:531–536 (Phila Pa 1976) CrossRefPubMed

Adams MA, Freeman BJ, Morrison HP, Nelson IW, Dolan P (2000) Mechanical initiation of intervertebral disc degeneration. Spine 25:1625–1636 (Phila Pa 1976) CrossRefPubMed

Roberts S, Evans H, Trivedi J, Menage J (2006) Histology and pathology of the human intervertebral disc. J Bone Joint Surg Am 2(88 Suppl):10–14

Biyani A, Andersson GBJ (2004) Low back pain: pathophysiology and management. J Am Acad Orthop Surg 12:106–115CrossRefPubMed

Shankar Hariharan, Scarlett Jeremy A, Abram Stephen E (2009) Anatomy and pathophysiology of intervertebral disc disease. Tech Reg Anesth Pain Manag 13:67–75CrossRef

Urban JP, McMullin JF (1988) Swelling pressure of the lumbar intervertebral discs: influence of age, spinal level, composition, and degeneration. Spine 13:179–187 (Phila Pa 1976) CrossRefPubMed

Di Martino A, Vaccaro AR, Yung Lee J, Denaro V, Lim MR (2005) Nucleus pulposus replacement: basic science and indications for clinical use. Spine 30(16 Suppl):S16–S22CrossRefPubMed

Di Martino A, Merlini L, Faldini C (2013) Autoimmunity in intervertebral disc herniation: from bench to bedside. Expert Opin Ther Targets 17(12):1461–1470CrossRefPubMed

Adams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine 31:2151–2161 (Phila Pa 1976) CrossRefPubMed

10.

Siepe CJ, Heider F, Wiechert K, Hitzl W, Ishak B, Mayer MH (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 PubMed

11.

Karppinen J, Shen FH, Luk KD, Andersson GB, Cheung KM, Samartzis D (2011) Management of degenerative disk disease and chronic low back pain. Orthop Clin North Am 42:513–528CrossRefPubMed

12.

Formica M, Cavagnaro L, Zanirato A, Felli L, Formica C (2016) Proximal junctional spondylodiscitis after pedicle subtraction osteotomy. Spine J 2:e49–e51. doi:10.1016/j.spinee.2015.09.050 CrossRef

13.

Punt IM, Visser VM, van Rhijn LW, Kurtz SM, Antonis J, Schurink GW, van Ooij A (2008) Complications and reoperations of the SB Charite lumbar disc prosthesis: experience in 75 patients. Eur Spine J 17:36–43CrossRefPubMed

14.

Formica M, Cavagnaro L, Basso M, Zanirato A, Felli L, Formica C (2015) Is it possible to preserve lumbar lordosis after hybrid stabilization? Preliminary results of a novel rigid-dynamic stabilization system in degenerative lumbar pathologies. Eur Spine J 24(Suppl 7):849–854. doi:10.1007/s00586-015-4264-8 CrossRefPubMed

15.

Thompson JP, Oegema TR, Bradford DS (1991) Stimulation of mature canine intervertebral disc by growth factors. Spine 16:253–260 (Phila Pa 1976); [PMID: 2028297] CrossRefPubMed

16.

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–S131CrossRefPubMed

17.

Masuda K (2008) Biological repair of the degenerated intervertebral disc by the injection of growth factors. Eur Spine J 17(Suppl 4):441–451CrossRefPubMedPubMedCentral

18.

Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K et al (2008) Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res 26(5):589–600CrossRefPubMed

19.

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

20.

Yang H, Wu J, Liu J, Ebraheim M, Castillo S, Liu X, Tang T, Ebraheim NA (2010) Transplanted mesenchymal stem cells with pure fibrinous gelatin-transforming growth factor-[beta]1 decrease rabbit intervertebral disc degeneration. Spine J 10:802–810CrossRefPubMed

21.

Emre TY, Atbasi Z, Demircioglu DT, Uzun M, Kose O (2016) Autologous osteochondral transplantation (mosaicplasty) in articular cartilage defects of the patellofemoral joint: retrospective analysis of 33 cases. Musculoskelet Surg. doi:10.1007/s12306-016-0448-6 PubMed

22.

D’Ambrosi R, Palumbo F, Paronzini A, Ragone V, Facchini RM (2016) Platelet-rich plasma supplementation in arthroscopic repair of full-thickness rotator cuff tears: a randomized clinical trial. Musculoskelet Surg 100(Suppl 1):25–32CrossRefPubMed

23.

Di Matteo B, Filardo G, Kon E, Marcacci M (2015) Platelet-rich plasma: evidence for the treatment of patellar and Achilles tendinopathy–a systematic review. Musculoskelet Surg 99(1):1–9. doi:10.1007/s12306-014-0340-1 CrossRefPubMed

24.

Felli L, Garlaschi G, Muda A, Tagliafico A, Formica M, Zanirato A, Alessio-Mazzola M (2016) Comparison of clinical, MRI and arthroscopic assessments of chronic ACL injuries, meniscal tears and cartilage defects. Musculoskelet Surg 100(3):231–238CrossRefPubMed

25.

Pettine K, Suzuki R, Sand T, Murphy M (2016) Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. Int Orthop 40(1):135–40. doi:10.1007/s00264-015-2886-4. [Epub 2015 Jul 10]

26.

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 212 CrossRefPubMed

27.

Orozco L, Soler R, Morera C, Alberca M, Sánchez A, García-Sancho J (2011) Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 92(7):822–828. doi:10.1097/TP.0b013e3182298a15 CrossRefPubMed

28.

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 35(11):E475–E480. doi:10.1097/BRS.0b013e3181cd2cf4 (Phila Pa 1976) CrossRefPubMed

29.

Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, Harrison JR, Gribbin CK, LaSalle EE, Nguyen JT, Solomon JL, Lutz GE (2016) Lumbar intradiskal platelet-rich plasma (PRP) injections: a prospective, double-blind, randomized controlled study. PM R 8(1):1–10; quiz 10. doi:10.1016/j.pmrj.2015.08.010. [Epub 2015 Aug 24]

30.

Levi D, Horn S, Tyszko S, Levin J, Hecht-Leavitt C, Walko E (2016) Intradiscal platelet-rich plasma injection for chronic discogenic low back pain: preliminary results from a prospective trial. Pain Med 17(6):1010–1022. doi: 10.1093/pm/pnv053 [Epub 2015 Dec 26]

31.

Akeda K, Imanishi T, Ohishi K, Masuda K, Uchida A, Sakakibara T, Kasai Y, Sudo A (2012) Intradiscal injection of autologous platelet-rich-plasma for the treatment of lumbar disc degeneration preliminary prospective clinical trial for discogenic low back pain patients. Poster No. 2194. ORS 2012 Annual Meeting

32.

Quattrocchi CC, Giona A, Di Martino A, Gaudino F, Mallio CA, Errante Y, Occhicone F, Vitali MA, Zobel BB, Denaro V (2015) Lumbar subcutaneous edema and degenerative spinal disease in patients with low back pain: a retrospective MRI study. Musculoskelet Surg. 99(2):159–163. doi:10.1007/s12306-015-0355-2 CrossRefPubMed

33.

Peng B, Wu W, Hou S, Li P, Zhang C, Yang Y (2005) The pathogenesis of discogenic low back pain. J Bone Jt Surg Br 87(1):62–67

34.

Formica M, Basso M, Cavagnaro L, Formica C, Zanirato A, Felli L (2016) Kümmell disease: illustrative case for definition criteria. Spine J 16(10):e707–e708. doi:10.1016/j.spinee.2016.03.035 CrossRefPubMed

35.

Formica M, Berjano P, Cavagnaro L, Zanirato A, Piazzolla A, Formica C (2014) Extreme lateral approach to the spine in degenerative and post traumatic lumbar diseases: selection process, results and complications. Eur Spine J 23(Suppl 6):684–692CrossRefPubMed

36.

Allain J, Delecrin J, Beaurain J, Poignard A, Vila T, Flouzat-Lachaniette CH (2014) Stand-alone ALIF with integrated intracorporeal anchoring plates in the treatment of degenerative lumbar disc disease: a prospective study on 65 cases. Eur Spine J 23(10):2136–2143CrossRefPubMed

37.

Cavagnaro L, Basso M, Alessio Mazzola M, Formica M (2014) Lumbar Traction in the management of low back pain: a survey of latest results. J Nov Physiother 4:5CrossRef

38.

Wegner I, Widyahening IS, van Tulder MW, Blomberg SE, de Vet HC (2013) Traction for low-back pain with or without sciatica. Cochrane Database Syst Rev 8(8). doi:10.1002/14651858.CD003010.pub5

39.

Wang Z, Perez-Terzic CM, Smith J, Mauck WD, Shelerud RA, Maus TP, Yang TH, Murad MH, Gou S, Terry MJ, Dauffenbach JP, Pingree MJ, Eldrige JS, Mohammed K, Benkhadra K, van Wijnen AJ, Qu W (2015) Efficacy of intervertebral disc regeneration with stem cells—A systematic review and meta-analysis of animal controlled trials. Gene 564(1):1–8CrossRefPubMed

40.

Depalma M (2012) Biologic treatments for discogenic low back pain. SpineLine 13(2):19–23

41.

Nishida K, Kang JD, Gilbertson LG, Moon SH, Suh JK, Vogt MT, Robbins PD, Evans CH (1999) Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene. Spine 24:2419–2425 (Phila Pa 1976) CrossRefPubMed

42.

Paul R, Haydon RC, Cheng H, Ishikawa A, Nenadovich N, Jiang W, Zhou L, Breyer B, Feng T, Gupta P, He TC, Phillips FM (2003) Potential use of Sox9 gene therapy for intervertebral degenerative disc disease. Spine 28:755–763 (Phila Pa 1976) PubMedPubMedCentral

43.

Wallach CJ, Kim JS, Sobajima S, Lattermann C, Oxner WM, McFadden K, Robbins PD, Gilbertson LG, Kang JD (2006) Safety assessment of intradiscal gene transfer: a pilot study. Spine J 6:107–112CrossRefPubMed

44.

Vadalà G, Sowa GA, Smith L, Hubert MG, Levicoff EA, Denaro V, Gilbertson LG, Kang JD (2007) Regulation of transgene expression using an inducible system for improved safety of intervertebral disc gene therapy. Spine 32:1381–1387 (Phila Pa 1976) CrossRefPubMed

45.

Tsaryk R, Gloria A, Russo T, Anspach L, De Santis R, Ghanaati S, Unger RE, Ambrosio L, Kirkpatrick CJ (2015) Collagen-low molecular weight hyaluronic acid semi-interpenetrating network loaded with gelatin microspheres for cell and growth factor delivery for nucleus pulposus regeneration. Acta Biomater 20:10–21CrossRefPubMed

46.

Mercuri J, Addington C, Pascal R, Gill S, Simionescu D (2014) Development and initial characterization of a chemically stabilized elastin glycosaminoglycan-collagen composite shape-memory hydrogel for nucleus pulposus regeneration. J Biomed Mater Res A 102:4380–4393PubMed

47.

Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement”. Cytotherapy 8(4):315–317CrossRefPubMed

48.

Alini M, Roughley PJ, Antoniou J, Stoll T, Aebi M (2002) A biological approach to treating disc degeneration: not for today, but maybe for tomorrow. Eur Spine J 11(Suppl 2):S215–S220PubMedPubMedCentral

49.

Mafi R, Hindocha S, Mafi P, Griffin M, Khan WS (2011) Sources of adult mesenchymal stem cells applicable for musculoskeletal applications—a systematic review of the literature. Open Orthop J 5:242–248CrossRefPubMedPubMedCentral

50.

Sobajima S, Vadala G, Shimer A, Kim JS, Gilbertson LG, Kang JD (2008) Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J 8(6):888–896CrossRefPubMed

51.

Gimble JM, Katz AJ, Bunnell BA (2007) Adipose-derived stem cells for regenerative medicine. Circ Res 100(9):1249–1260CrossRefPubMed

52.

Longo UG, Papapietro N, Petrillo S, Franceschetti E, Maffulli N, Denaro V (2012) Mesenchymal stem cell for prevention and management of intervertebral disc degeneration. Stem Cells Int 2012. doi:10.1155/2012/921053

53.

Strassburg S, Richardson SM, Freemont AJ, Hoyland JA (2010) Co-culture induces mesenchymal stem cell differentiation and modulation of the degenerate human nucleus pulposus cell phenotype. Regen Med 5(5):701–711CrossRefPubMed

54.

Serigano K, Sakai D, Hiyama A, Tamura F, Tanaka M, Mochida J (2010) Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. J Orthop Res 28:1267–1275CrossRefPubMed

55.

Sakai D, Nishimura K, Tanaka M, Nakajima D, Grad S, Alini M, Kawada H, Ando K, Mochida J. (2015) Migration of bone marrow-derived cells for endogenous repair in a new tail-looping disc degeneration model in the mouse: a pilot study. Spine J 15(6):1356–65. doi:10.1016/j.spinee.2013.07.491 [Epub 2014 Nov 24]

56.

Yim RL, Lee JT, Bow CH, Meij B, Leung V, Cheung KM, Vavken P, Samartzis D (2014) A systematic review of the safety and efficacy of mesenchymal stem cells for disc degeneration: insights and future directions for regenerative therapeutics. Stem Cells 23(21):2553–67. doi:10.1089/scd.2014.0203 [Epub. Review]

57.

Kim DJ, Moon SH, Kim H, Kwon UH, Park MS, Han KJ, Hahn SB, Lee HM (2003) Bone morphogenetic protein-2 facilitates expression of chondrogenic, not osteogenic, phenotype of human intervertebral disc cells. Spine 28:2679–2684. doi:10.1097/01.BRS.0000101445.46487.16 (Phila Pa 1976); [PMID: 14673369] CrossRefPubMed

58.

Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, Aebi M, Alini M (1996) The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest 98:996–1003. doi:10.1172/JCI118884 [PMID: 8770872] CrossRefPubMedPubMedCentral

59.

Masuda K, Oegema TR, An HS (2004) Growth factors and treatment of intervertebral disc degeneration. Spine 29:2757–2769. doi:10.1097/01.brs.0000146048.14946.af (Phila Pa 1976); [PMID: 15564925] CrossRefPubMed

60.

Chen WH, Liu HY, Lo WC, Wu SC, Chi CH, Chang HY, Hsiao SH, Wu CH, Chiu WT, Chen BJ, Deng WP (2009) Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biomaterials 30(29):5523–5533CrossRefPubMed

61.

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

62.

Akeda K, An HS, Pichika R, Attawia M, Thonar EJ, Lenz ME, Uchida A, Masuda K (2006) Platelet-rich plasma (PRP) stimulates the extracellular matrix metabolism of porcine nucleus pulposus and anulus fibrosus cells cultured in alginate beads. Spine 31(9):959–966 (Phila Pa 1976) CrossRefPubMed

63.

Formica M, Cavagnaro L, Formica C, Mastrogiacomo M, Basso M, Di Martino (2015) What is the preclinical evidence on platelet rich plasma and intervertebral disc degeneration? A. Eur Spine J 24(11):2377–86. doi:10.1007/s00586-015-4189-2 [Epub 2015 Aug 14]

Title: What is the clinical evidence on regenerative medicine in intervertebral disc degeneration?
Authors: M. Basso
L. Cavagnaro
A. Zanirato
S. Divano
C. Formica
M. Formica
L. Felli
Publication date: 01-08-2017
Publisher: Springer Milan
Published in: MUSCULOSKELETAL SURGERY / Issue 2/2017
Print ISSN: 2035-5106
Electronic ISSN: 2035-5114
DOI: https://doi.org/10.1007/s12306-017-0462-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

What is the clinical evidence on regenerative medicine in intervertebral disc degeneration?

Abstract

Purpose

Materials and methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Materials and methods

Results

Conclusions

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