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REGENERATIVE CAPACITY OF INTERVERTEBRAL DISC CHONDROCYTES FOLLOWING AUTOLOGOUS DISC CHONDROCYTE TRANSPLANTATION IN A CANINE MODEL



Abstract

Study Design: Experimental study in dogs:

Objective: To assess the efficiency of disc chondrocyte transplantation in a canine model.

Summary of Background Data: Conventional clinical treatments of intervertebral disc herniation and degeneration are focused on excision of damaged tissue, stabilization, and spinal fusion. The development and refinement of cell-based therapeutics for tissue regeneration and repair have spawned a multitude of applications including autologous disc chondrocyte transplantation. For clinical application the efficiency of disc chondrocyte transplantation was assessed using a pre-clinical canine model to show the technical feasibility and biological relevance for disc repair and retardation of disc degeneration. This report examined the protein expression of transplanted disc chondrocytes and their role in the clinically observed disc repair following autologous disc chondrocyte transplantation.

Methods: The nucleus and inner annulus were sampled from four skeletally-mature dogs by micro-discectomy. Disc chondrocytes were isolated and propagated under GMP validated conditions including completely autologous serum conditions. Two months later, the cultured cells were transplanted through the contralateral side of experimental discs after testing complete healing of the annulus by measuring intradiscal pressure stability. After seven months the animals were humanely killed. One half of the vertically halved lumbar spines were embedded in paraffin and sections were analysed histologically and immunohistochemically.

Results: Histological examinations revealed large clusters of cells within the nucleus area of the treated discs. Cells within these cell clones were found to be viable and surrounded by de novo synthesized matrix as evidenced by a distinct histological staining and immunohistochemical expression pattern. A disc-specific expression of collagen type I and II and hyaline-specific proteoglycans was observed indicating the regenerative and reconstructive capacity of the transplanted disc chondrocytes.

Conclusions: These results indicate the contribution of transplanted disc chondrocytes to the observed clinical success of this cell-based therapy.

These abstracts were prepared by Mr. Brian J C Freeman FRCS (Tr & Orth). Correspondence should be addressed to him at The Centre for Spinal Studies and Surgery, University Hospital, Queens Medical Centre, Nottingham NG7 2UH.