Disc Chondrocyte Transplantation in a Canine Model: A Treatment for Degenerated or Damaged Intervertebral Disc

Ganey, Timothy; Libera, Jeanette; Moos, Verena; Alasevic, Olivera; Fritsch, Karl-Gerd; Meisel, Hans; Hutton, William

doi:10.1097/01.brs.0000097891.63063.78

Cited by 212 publications

(143 citation statements)

References 31 publications

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“…1,2,10,16,20,22,25,[30][31][32][34][35][36][37][38]46,48,49,53,54,56,57,60,62,[64][65][66][67]69,73,83,90 The EuroDISC study, by Meisel and colleagues, 49 investigated the percutaneous transplantation of autologous disc chondrocytes. Following microdiscectomy, disc chondrocytes were harvested and expanded in vitro and were subsequently injected into the NP 3 months postoperatively.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Oehme

Ghosh

Shimmon

et al. 2014

SPI

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Object Following microdiscectomy, discs generally fail to undergo spontaneous regeneration and patients may experience chronic low-back pain and recurrent disc prolapse. In published studies, formulations of mesenchymal progenitor cells combined with pentosan polysulfate (MPCs+PPS) have been shown to regenerate disc tissue in animal models, suggesting that this approach may provide a useful adjunct to microdiscectomy. The goal of this preclinical laboratory study was to determine if the transplantation of MPCs+PPS, embedded in a gelatin/fibrin scaffold (SCAF), and transplanted into a defect created by microdiscectomy, could promote disc regeneration. Methods A standardized microdiscectomy procedure was performed in 18 ovine lumbar discs. The subsequent disc defects were randomized to receive either no treatment (NIL), SCAF only, or the MPC+PPS formulation added to SCAF (MPCs+PPS+SCAF). Necropsies were undertaken 6 months postoperatively and the spines analyzed radiologically (radiography and MRI), biochemically, and histologically. Results No adverse events occurred throughout the duration of the study. The MPC+PPS+SCAF group had significantly less reduction in disc height compared with SCAF-only and NIL groups (p < 0.05 and p < 0.01, respectively). Magnetic resonance imaging Pfirrmann scores in the MPC+PPS+SCAF group were significantly lower than those in the SCAF group (p = 0.0213). The chaotropic solvent extractability of proteoglycans from the nucleus pulposus of MPC+PPS+SCAF-treated discs was significantly higher than that from the SCAF-only discs (p = 0.0312), and using gel exclusion chromatography, extracts from MPC+PPS+SCAF-treated discs also contained a higher percentage of proteoglycan aggregates than the extracts from both other groups. Analysis of the histological sections showed that 66% (p > 0.05) of the MPC+PPS+SCAF-treated discs exhibited less degeneration than the NIL or SCAF discs. Conclusions These findings demonstrate the capacity of MPCs in combination with PPS, when embedded in a gelatin sponge and sealed with fibrin glue in a microdiscectomy defect, to restore disc height, disc morphology, and nucleus pulposus proteoglycan content.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Oehme

Ghosh

Shimmon

et al. 2014

SPI

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“…When cell therapy was hailed as the next generation treatment, another approach to regenerative therapy, autologous nucleus pulposus cell transplantation, also became a major research topic in the context of the regeneration of IVDs (Okuma et al 2000;Ganey et al 2003;Gruber et al 2002;Nishimura and Mochida 1998;Nomura et al 2001). However, because the supply of autologous IVD cells is problematic (Okano 2002), the notion of using stem cells in this context has increased in importance, and trials are currently in progress (Crevensten et al 2004;Leung et al 2006;Sakai et al 2006Sakai et al , 2005Sakai et al , 2003.…”

Section: Introductionmentioning

confidence: 99%

Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat

et al. 2009

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In this study, the authors explored the effect of human mesenchymal stem cell (MSC) implantation on the restoration of degenerative intervertebral discs (IVDs) in the rat. A unique rat coccygeal model was used to investigate the effects of transplanting human MSCs and to examine MSC survival in degenerative discs. MSC implantations into rat coccygeal IVDs were performed at 2 weeks postinjury. Radiologic and histologic evaluations were performed at 2, 4, 6, and 8 weeks post-injury. MSCinjected segments (TS) retained disc height and signal intensity, but injured non-injected segment (IS) progressively lost disc height. Pathological results revealed that the TS group showed relative restoration of the inner annulus structure; however, the IS group showed destruction of the inner annulus structure. Immunohistochemical staining using Anti-Human Nucleic Antibody (#MAB1281 Chemicon) revealed positive staining in the TS group at 2 weeks posttransplantation (4 weeks post-injury). This study shows that human MSCs survive for 2 weeks after transplantation into the IVDs of rats, and that MSCs increased the heights and signal intensities of intervertebral disc.

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“…Of the cells to use for cell-based therapies for IVD degeneration, IVD cells themselves are the least likely candidates for use given the difficulty of harvesting sufficient numbers of viable autologous disc cells from symptomatic IVDs [112-114, 116, 117]. However, a number of cell types have provided promising results in therapeutic cell replacement strategies for disc repair, including costal and articular chondrocytes [30,55,73,111], auricular chondrocytes [33] and mesenchymal stem cells (MSCs) [3,41,113,114,117,123,132]. A common pathological features of IVD degeneration is a chondroid metaplasia of the NP with clusters (chondrones) of chondrocyte-like cells within a dense hyaline-like matrix [59] which is different from the fibrocartilage of the normal NP.…”

Section: Cell-based Therapies For the Biologic Treatment Of Disc Degementioning

confidence: 99%

Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

et al. 2008

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The objective of this study was to assess the impact of a landmark annular lesion model on our understanding of the etiopathogenesis of IVD degeneration and to appraise current IVD repairative strategies. A number of studies have utilised the Osti sheep model since its development in 1990. The experimental questions posed at that time are covered in this review, as are significant recent advances in annular repair strategies. The ovine model has provided important spatial and temporal insights into the longitudinal development of annular lesions and how they impact on other discal and paradiscal components such as the NP, cartilaginous end plates, zygapophyseal joints and vertebral bone and blood vessels. Important recent advances have been made in biomatrix design for IVD repair and in the oriented and dynamic culture of annular fibrochondrocytes into planar, spatially relevant, annular type structures.

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Disc Chondrocyte Transplantation in a Canine Model: A Treatment for Degenerated or Damaged Intervertebral Disc

Abstract: Autologous chondrocyte transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration.

Cited by 212 publications

References 31 publications

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat

Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

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