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Folia Neuropathologica
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vol. 56
Original paper

Evaluation of regenerative processes in the pig model of intervertebral disc degeneration after transplantation of bone marrow-derived mesenchymal stem cells

Monika Barczewska, Katarzyna Jezierska-Wozniak, Aleksandra Habich, Seweryn Lipinski, Piotr Holak, Wojciech Maksymowicz, Joanna Wojtkiewicz

Folia Neuropathol 2018; 56 (2): 124-132
Online publish date: 2018/06/28
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The pathophysiology of degenerative disc disease (DDD) is complex and not fully understood. While surgical treatment and appropriate rehabilitation offer relief of acute symptoms, there is a need to find tissue engineering strategies for intervertebral disc repair to restore healthy higher and histological structure. The purpose of this study was to estimate the survival rate of transplanted cells and their post-delivery integration level at the damage site.

Material and methods
We used an in vivo porcine model to investigate autogenic bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation for intervertebral disc repair. In our experiment we used a large animal model of DDD induced by percutaneous laser light deliveries. The percutaneous approach has also been used for delivery of BM-MSCs into the intervertebral disc space.

After MSC transplantation, we observed a deceleration of the degenerative process in the intervertebral disc, relative to degenerative discs without MSC transplantation.

By using a large animal model that mimicked the development of intervertebral degenerative disc disease, the present results are indicative of the clinical feasibility of this procedure.


disc disease, intervertebral disc regeneration, stem cells, regenerative medicine, porcine model

Acosta FL, Metz L, Adkisson HD, Liu J, Carruthers-Liebenberg E, Milliman C, Maloney M, Lotz JC. Porcine intervertebral disc repair using allogenic juvenile articular chondrocytes or mesenchymal stem cells. Tissue Eng Part A 2011; 17: 3045-3055.
Alini M, Eisenstein SM, Ito K, Little C, Kettler AA, Masuda K, Melrose J, Ralphs J, Stokes I, Wilke HJ. Are animal models useful for studying human disc disorders/degeneration? Eur Spine J 2008; 17: 2-19.
An HS, Takegami K, Kamada H, Nguyen CM, Thonar EJ, Singh K, Andersson GB, Masuda K. Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine (Phila Pa 1976) 2005; 30: 25-31.
Andersson G. Epidemiological features of chronic low back pain. Lancet 1999; 354: 581-585.
Barczewska M, Wojtkiewicz J, Habich A, Janowski M, Adamiak Z, Holak P, Matyjasik H, Bulte JW, Maksymowicz W, Walczak. MR monitoring of minimally invasive delivery of mesenchymal stem cells into the porcine intervertebral disc. PLoS One 2013; 8: e74658.
Bendtsen M, Bünger CE, Zou X, Foldager C, Jørgensen HS. Autologous stem cell therapy maintains vertebral blood flow and contrast diffusion through the endplate in experimental intervertebral disc degeneration. Spine (Phila Pa 1976) 2011; 36: E373-E379.
Brisby H. Pathology and possible mechanisms of nervous system response to disc degeneration. J Bone Joint Surg Am 2006; 88 Suppl 2: 68-71.
Buckwalter JA. Aging and degeneration of the human intervertebral disc. Spine (Phila Pa 1976) 1995; 20: 1307-1314.
Cai F, Wu XT, Xie XH, Wang F, Hong X, Zhuang SY, Zhu L, Rui YF, 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 2015; 39: 149-159.
Chen WH, Liu HY, Lo WC, Wu SC, Chi CH, Chang HY, Hsiao SH, Wu CH, Chiu WT, Chen BJ, Deng WP. Intervertebraldisc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biomaterials 2009; 30: 5523-5533.
Clouet J, Pot-Vaucel M, Grimandi G, Masson M, Lesoeur J, Fellah BH, Gauthier O, Fusellier M, Cherel Y, Maugars Y, Guicheux J, Vinatier C. Characterization of the age-dependent intervertebral disc changes in rabbit by correlation between MRI, histology and gene expression. BMC Musculoskelet Disord 2011; 12: 147.
Collin EC, Grad S, Zeugolis DI, Vinatier CS, Clouet JR, Guicheux JJ, Weiss P, Alini M, Pandit AS. An injectable vehicle for nucleus pulposus cell-based therapy. Biomaterials 2001; 32: 2862-2870.
Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, Berven S. Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 2004; 32: 430-434.
Feng G, Zhao X, Liu H, Zhang H, Chen X, Shi R, Liu X, Zhao X, Zhang W, Wang B. Transplantation of mesenchymal stem cells and nucleus pulposus cells in a degenerative disc model in rabbits: a comparison of 2 cell types as potential candidates for disc regeneration. J Neurosurg Spine 2011; 14: 322-329.
Gimble JM, Guilak F. Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 2003; 5: 362-369.
Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res 2007; 100: 1249-1260.
Ghosh P, Moore R, Vernon-Roberts B, Goldschlager T, Pascoe D, Zannettino A, Gronthos S, Itescu S. Immunoselected STRO-3+ mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs. J Neurosurg Spine 2012; 16: 479-488.
Gorensek M, Joksimovic C, Kregar-Velikonja N Gorensek M, Knezevic M, Jeras M, Pavlovcic V, Cör A. Nucleus pulposus repair with cultured autologous elastic cartilage derived chondrocytes. Cell Mol Biol Lett 2004; 9:363-373.
Grisendi G, Annerén C, Cafarelli L, Sternieri R, Veronesi E, Cervo GL, Luminari S, Maur M, Frassoldati A, Palazzi G, Otsuru S, Bambi F, Paolucci P, Pierfranco C, Horwitz E, Dominici M. GMP-manufactured density gradient media for optimized mesenchymal stromal/stem cell isolation and expansion. Cytotherapy 2010; 12: 466-477.
Guter CC, See EY, Blanquer SB, Pandit A, Ferguson SJ, Benneker LM, Grijpma DW, Sakai D, Eglin D, Alini M, Iatridis JC, Grad S. Challenges and strategies in the repair of ruptured annulus fibrosus. Eur Cell Mater 2013; 2: 1-21.
Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K, Tamura F, Sakai D. Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res 2008; 26: 589-600.
Henriksson HB, Svanvik T, Jonsson M, Hagman M, Horn M, Lindahl A, Brisby H. Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model. Spine (Phila Pa 1976) 2009; 34: 141-148.
Ho G, Leung VYL, Cheung KMC, Chan D. Effect of severity of intervertebral disc injury on mesenchymal stem cell-based regeneration. Connect Tissue Res 2008; 49: 15-21.
Hohaus C, Ganey TM, Minkus Y, Meisel HJ. Cell transplantation in lumbar spine disc degeneration disease. Eur Spine J 2008; 17: 492-503.
Jezierska-Wozniak K, Barczewska M, Habich A, Wojtacha P, Badowska W, Maksymowicz W, Wojtkiewicz J. The feasibility of the CD271+ and CD271- mesenchymal stromal cell enrichment toward nucleus pulposus-like cells. Folia Histochem Cytobiol 2017; 55: 114-123.
Leung VYL, Chan D, Cheung KMC. Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction. Eur Spine J 2006; 15 Suppl 3: S406-S413.
Lilliefors HW. On the Kolmogorov-Smirnov test for normality with mean and variance unknown. J Am Stat Assoc 1967; 62: 399-402.
Lipiński S, Jezierska-Woźniak K, Habich A, Barczewska M, Wojtkiewicz J, Walczak P, Maksymowicz W. Methodology for Assessing the Degree of Degeneration of the Porcine Intervertebral Discs Based on Magnetic Resonance Imaging. IFMBE Proceedings 2016; 53: 399-402.
Lotz JC. Animal models of intervertebral disc degeneration: lessons learned. Spine (Phila Pa 1976) 2004; 29: 2742-2750.
Luoma K, Vehmas T, Riihimäki H, Raininko R. Disc height and signal intensity of the nucleus pulposus on magnetic resonance imaging as indicators of lumbar disc degeneration. Spine (Phila Pa 1976) 2001; 26: 680-686.
Modic MT, Masaryk TJ, Ross JS, Carter JR. Imaging of degenerative disk disease. Radiology 2001; 168: 177-186.
Nishimura K, Mochida J. Percutaneous reinsertion of the nucleus pulposus: an experimental study. Spine (Phila Pa 1976) 1998; 23: 1531-1538.
Nomura T, Mochida J, Okuma M, Nishimura K, Sakabe K. Nucleus pulposus allograft retards intervertebral disc degeneration. Clin Orthop Relat Res 2001; 389: 94-101.
Oehme D, Ghosh P, Shimmon S, Wu J, McDonald C, Troupis JM, Goldschlager T, Rosenfeld JV, Jenkin G. Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model. J Neurosurg Spine 2014; 20: 657-669
Orozco L, Soler R, Morera C, Alberca M, Sánchez A, García-Sancho J. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 2001; 92: 822-828.
Osti OL, Vernon-Roberts B, Moore R, Fraser RD. Annular tears and disc degeneration in the lumbar spine. A post mortem study of 135 discs. J Bone Joint Surg 1992; 74: 678-882.
Pfirrmann CW, Metzdorf A, Elfering A, Hodler J, Boos N. Effect of aging and degeneration on disc volume and shape: a quantitative study in asymptomatic volunteers. J Orthop Res 2006; 24: 1086-1094.
Richardson SM, Walker RV, Parker S, Rhodes NP, Hunt JA, Freemont AJ, Hoyland JA. Intervertebral disc cell-mediated mesenchymal stem cell differentiation. Stem Cells 2006; 24: 707-716.
Risbud MV, Albert TJ, Guttapalli A, Vresilovic EJ, Hillibrand AS, Vaccaro AR, Shapiro IM. Differentiation of mesenchymal stem cells towards a nucleus pulposus-like phenotype in vitro: implications for cell-based transplantation therapy. Spine (Phila Pa 1976) 2004; 29: 2627-2632.
Rosenberg LJ. Chemical basis for the histological use of safranin O in the study of articular cartilage. Bone Joint Surg Am 1971; 53: 69-82.
Roberts S, Eisenstein SM, Menage J, Evans EH, Ashton IK. Mechanoreceptors in intervertebral discs. Morphology, distribution, and neuropeptides. Spine (Phila Pa 1976) 1995; 20: 2645-2651.
Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T. Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine (Phila Pa 1976) 2005; 30: 2379-2387.
Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M, Nakai T, Ando K, Hotta T. Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 2006: 27: 335-345.
Serigano K, Sakai D, Hiyama A, Tamura F, Tanaka M, Mochida J. Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. J Orthop Res 2010; 28: 1267-1275.
Sobajima S, Vadala G, Shimer A, Kim JS, Gilbertson LG, Kang JD. Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J 2008; 8: 888-896.
Steck E, Bertram H, Abel R, Chen B, Winter A, Richter W. Induction of intervertebral disc-like cells from adult mesenchymal stem cells. Stem Cells 2005; 23: 403-411.
Subhan RA, Puvanan K, Murali MR, Raghavendran HR, Shani S, Abdullah BJ, Abbas AA, Mohamed JA, Kamarul T. Fluoroscopy assisted minimally invasive transplantation of allogenic mesenchymal stromal cells embedded in HyStem reduces the progression of nucleus pulposus degeneration in the damaged interverbal disc: a preliminary study in rabbits. Sci World J 2014; 2014: 818502.
Thompson JP, Oegema TR, Bradford DS. Stimulation of mature canine intervertebral disc by growth factors. Spine (Phila Pa 1976) 1991; 16: 253-260.
Walsh AJL, Bradford DS, Lotz JC. In Vivo growth factor treatment of degenerated intervertebral discs. Spine (Phila Pa 1976) 2004; 29: 156-163.
Vadala G, Studer RK, Sowa G, Spiezia F, Iucu C, Denaro V, Gilbert­son LG, Kang JD. Coculture of bone marrow mesenchymal stem cells and nucleus pulposus cells modulate gene expression profile without cell fusion. Spine (Phila Pa 1976) 2008; 33: 870-876.
Yamamoto Y, Mochida J, Sakai D, Nakai T, Nishimura K, Kawada H, Hotta T. Upregulation of the viability of nucleus pulposus cells by bone marrowderived stromal cells: significance of direct cell-to-cell contact in co-culture system. Spine (Phila Pa 1976) 2004; 29: 1508-1514.
Yang X, Li X. Nucleus pulposus tissue engineering: a brief review. Eur Spine J 2009; 18: 1564-1572.
Yang F, Leung VYL, Luk KDK, Chan D, Cheung KMC. Mesenchymal stem cells arrest intervertebral disc degeneration through chondrocytic differentiation and stimulation of endogenous cells. Mol Ther 2009; 17: 1959-1966.
Yoshikawa T, Ueda Y, Miyazaki K, Koizumi M, Takakura Y. Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine (Phila Pa 1976) 2010; 35: E475-E480.
Zhang Y, Drapeau S, Howard SA, Thonar EJ, Anderson DG. Transplantation of goat bone marrow stromal cells to the degenerating intervertebral disc in a goat disc injury model. Spine (Phila Pa 1976) 2011; 36: 372-377.
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