Intervertebral disc regeneration using platelet‑rich plasma‑containing bone marrow‑derived mesenchymal stem cells: A preliminary investigation

Wang,Shan‑Zheng; Jin,Ji‑Yang; Guo,Yu‑Dong; Ma,Liang‑Yu; Chang,Qing; Peng,Xin‑Gui; Guo,Fang‑Fang; Zhang,Hai‑Xiang; Hu,Xin‑Feng; Wang,Chen

doi:10.3892/mmr.2016.4983

Intervertebral disc regeneration using platelet‑rich plasma‑containing bone marrow‑derived mesenchymal stem cells: A preliminary investigation

Authors:
- Shan‑Zheng Wang
- Ji‑Yang Jin
- Yu‑Dong Guo
- Liang‑Yu Ma
- Qing Chang
- Xin‑Gui Peng
- Fang‑Fang Guo
- Hai‑Xiang Zhang
- Xin‑Feng Hu
- Chen Wang
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Affiliations: Department of Orthopaedics, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China, Department of Plastic Surgery, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China, Department of Orthopaedics, Qidong People's Hospital, Qidong, Jiangsu 226200, P.R. China
Published online on: March 7, 2016 https://doi.org/10.3892/mmr.2016.4983
Pages: 3475-3481
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Platelet‑rich plasma (PRP) is a promising strategy for intervertebral disc degeneration (IDD). However, the short half‑life of growth factors released from PRP cannot continuously stimulate the degenerated discs. Thus, the present study hypothesized that the combined use of PRP and bone marrow‑derived mesenchymal stem cells (BMSCs) may repair the early degenerated discs in the long term for their synergistic reparative effect. In the present study, following the induction of early IDD by annular puncture in rabbits, PRP was prepared and mixed with BMSCs (PRP‑BMSC group) for injection into the early degenerated discs. As controls, phosphate‑buffered saline (PBS; PBS group) and PRP (PRP group) were similarly injected. Rabbits without any intervention served as a control group. At 8 weeks following treatment, histological changes of the injected discs were assessed. Magnetic resonance imaging (MRI) was used to detect the T2‑weighted signal intensity of the targeted discs at weeks 1, 2 and 8 following treatment. Annular puncture resulted in disc narrowing and decreased T2‑weighted signal intensity. At weeks 1 and 3, MRI examinations showed regenerative changes in the PRP‑BMSC group and PRP group, whereas the PBS group exhibited a continuous degenerative process of the discs. At 8 weeks post‑injection, the PRP‑BMSCs induced a statistically significant restoration of discs, as shown by MRI (PRP‑BMSCs, vs.PRP and PBS; P<0.05), which was also confirmed by histological evaluations. Thus, compared with PRP, the administration of PRP‑containing BMSCs resulted in a superior regenerative effect on the early degenerated discs, which may be a promising therapeutic strategy for the restoration of early degenerated discs.

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1	Dagenais S, Caro J and Haldeman S: A systematic review of low back pain cost of illness studies in the United States and internationally. Spine J. 8:8–20. 2008. View Article : Google Scholar : PubMed/NCBI
2	McBeth J and Jones K: Epidemiology of chronic musculoskeletal pain. Best Pract Res Clin Rheumatol. 21:403–425. 2007. View Article : Google Scholar : PubMed/NCBI
3	Mirza SK and Deyo RA: Systematic review of randomized trials comparing lumbar fusion surgery to nonoperative care for treatment of chronic back pain. Spine. 32:816–823. 2007. View Article : Google Scholar : PubMed/NCBI
4	Karppinen J, Shen FH, Luk KD, Andersson GB, Cheung KM and Samartzis D: Management of degenerative disk disease and chronic low back pain. Orthop Clin North Am. 42:513–528. 2011. View Article : Google Scholar : PubMed/NCBI
5	Zhang Y, Chee A, Thonar EJ and An HS: Intervertebral disk repair by protein, gene, or cell injection: a framework for rehabilitation-focused biologics in the spine. PM R. 3(6 Suppl 1): S88–S94. 2011. View Article : Google Scholar : PubMed/NCBI
6	Masuda K: Biological repair of the degenerated intervertebral disc by the injection of growth factors. Eur Spine J. 17(Suppl 4): S441–S451. 2008. View Article : Google Scholar
7	Xie X, Zhang C and Tuan RS: Biology of platelet-rich plasma and its clinical application in cartilage repair. Arthritis Res Ther. 16:2042014. View Article : Google Scholar : PubMed/NCBI
8	Finnson KW, McLean S, Di Guglielmo GM and Philip A: Dynamics of transforming growth factor beta signaling in wound healing and scarring. Adv Wound Care (New Rochelle). 2:195–214. 2013. View Article : Google Scholar
9	Spencer EM, Tokunaga A and Hunt TK: Insulin-like growth factor binding protein-3 is present in the alpha-granules of platelets. Endocrinology. 132:996–1001. 1993.PubMed/NCBI
10	Longo UG, Petrillo S, Franceschetti E, Maffulli N and Denaro V: Growth factors and anticatabolic substances for prevention and management of intervertebral disc degeneration. Stem Cells Int. 2012:8971832012.PubMed/NCBI
11	Wang SZ, Rui YF, Tan Q and Wang C: Enhancing intervertebral disc repair and regeneration through biology: Platelet-rich plasma as an alternative strategy. Arthritis Res Ther. 15:2202013. View Article : Google Scholar : PubMed/NCBI
12	Marx RE: Platelet-rich plasma (PRP): What is PRP and what is not PRP? Implant Dent. 10:225–228. 2001. View Article : Google Scholar
13	Huang YC, Leung VY, Lu WW and Luk KD: The effects of microenvironment in mesenchymal stem cell-based regeneration of intervertebral disc. Spine J. 13:352–362. 2013. View Article : Google Scholar : PubMed/NCBI
14	Benneker LM, Andersson G, Iatridis JC, Sakai D, Härtl R, Ito K and Grad S: Cell therapy for intervertebral disc repair: Advancing cell therapy from bench to clinics. Eur Cell Mater. 27:5–11. 2014.PubMed/NCBI
15	Ikehara S and Li M: Stem cell transplantation improves aging-related diseases. Front Cell Dev Biol. 2:162014. View Article : Google Scholar : PubMed/NCBI
16	Sakai D: Stem cell regeneration of the intervertebral disk. Orthop Clin North Am. 42:555–562. 2011. View Article : Google Scholar : PubMed/NCBI
17	Cai F, Wu XT, Xie XH, Wang F, Hong X, Zhuang SY, Zhu L, Rui YF and Shi R: Evaluation of intervertebral disc regeneration with implantation of bone marrow mesenchymal stem cells (BMSCs) using quantitative T2 mapping: A study in rabbits. Int Orthop. 39:149–159. 2015. View Article : Google Scholar
18	Schilling T, Nöth U, Klein-Hitpass L, Jakob F and Schütze N: Plasticity in adipogenesis and osteogenesis of human mesenchymal stem cells. Mol Cell Endocrinol. 271:1–17. 2007. View Article : Google Scholar : PubMed/NCBI
19	Landesberg R, Roy M and Glickman RS: Quantification of growth factor levels using a simplified method of platelet-rich plasma gel preparation. J Oral Maxillofac Surg. 58:297–300. 2000. View Article : Google Scholar : PubMed/NCBI
20	Masuda K, Aota Y, Muehleman C, Imai Y, Okuma M, Thonar EJ, Andersson GB and An HS: A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: Correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine (Phila Pa 1976). 30:5–41. 2005. View Article : Google Scholar
21	Thompson JP, Pearce RH, Schechter MT, Adams ME, Tsang IK and Bishop PB: Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc. Spine. 15:411–415. 1990. View Article : Google Scholar : PubMed/NCBI
22	Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J and Boos N: Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine. 26:1873–1878. 2001. View Article : Google Scholar : PubMed/NCBI
23	Zhang Y, Chee A, Thonar EJ and An HS: Intervertebral disk repair by protein, gene, or cell injection: A framework for rehabilitation-focused biologics in the spine. PM R. 3(6 Suppl 1): S88–S94. 2011. View Article : Google Scholar : PubMed/NCBI
24	Fréchette JP, Martineau I and Gagnon G: Platelet-rich plasmas: Growth factor content and roles in wound healing. J Dent Res. 84:434–439. 2005. View Article : Google Scholar : PubMed/NCBI
25	Abrams GD, Frank RM, Fortier LA and Cole BJ: Platelet-rich plasma for articular cartilage repair. Sports Med Arthrosc. 21:213–219. 2013. View Article : Google Scholar : PubMed/NCBI
26	Wang SZ, Rui YF, Lu J and Wang C: Cell and molecular biology of intervertebral disc degeneration: Current understanding and implications for potential therapeutic strategies. Cell Prolif. 47:381–390. 2014. View Article : Google Scholar : PubMed/NCBI
27	Xie X, Wang Y, Zhao C, Guo S, Liu S, Jia W, Tuan RS and Zhang C: Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials. 33:7008–7018. 2012. View Article : Google Scholar : PubMed/NCBI
28	Strassburg S, Richardson SM, Freemont AJ and Hoyland JA: Co-culture induces mesenchymal stem cell differentiation and modulation of the degenerate human nucleus pulposus cell phenotype. Regen Med. 5:701–711. 2010. View Article : Google Scholar : PubMed/NCBI
29	Obata S, Akeda K, Imanishi T, Masuda K, Bae W, Morimoto R, Asanuma Y, Kasai Y, Uchida A and Sudo A: Effect of autologous platelet-rich plasma-releasate on intervertebral disc degeneration in the rabbit anular puncture model: A preclinical study. Arthritis Res Ther. 14:R2412012. View Article : Google Scholar : PubMed/NCBI
30	Nagae M, Ikeda T, Mikami Y, Hase H, Ozawa H, Matsuda K, Sakamoto H, Tabata Y, Kawata M and Kubo T: Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng. 13:147–158. 2007. View Article : Google Scholar : PubMed/NCBI
31	Sawamura K, Ikeda T, Nagae M, Okamoto S, Mikami Y, Hase H, Ikoma K, Yamada T, Sakamoto H, Matsuda K, et al: 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. 2009. View Article : Google Scholar : PubMed/NCBI