Summary

PCA-III, a phosphocitrate analog, acts not only as a potent calcification inhibitor but also as a protective agent for extracellular matrices. PCA-III has potential as a disease-modifying drug in the treatment of primary osteoarthritis and posttraumatic osteoarthritis in humans.

Introduction: Eighty percent of individuals experience low back pain in their lifetime. This is often due to disc injury or degeneration. Conservative treatment of discogenic pain is often unsuccessful whilst surgery with the use of spacers or fusion is non-physiological.

Aim: To develop an animal model to assess the viability of autologous disc cell therapy.

Methods: The fat sand rat (Psammomys obesus obesus) was chosen because of its predisposition to the early development of spondylosis. Using microsurgical techniques fragments of annulus and nucleus were harvested from a single disc in 50 sand rats. Vascular clips were placed on the adjacent psoas muscle to mark the harvested level. Disc material was initially cultured in a monolayer then transferred into a three-dimensional culture medium of agarose. This technique yields greater cellular proliferation and the development of cell growth in colonies. Cells were labelled with bromodeoxyuridine for later immunohistochemical identification. Twenty thousand cells in a carrier medium were then reimplanted at a second operation at an adjacent disc level in the same animal. The rat was subsequently sacrificed and the histology of the disc space was reviewed.

Results: To date, 50 primary disc harvests and 30 reimplantations have been performed. Two rats died prior to reimplantation. All histological specimens confirmed the presence of viable transplanted disc cells.

Conclusions: Autologous disc cell transplantation can be performed in the rat. Further modification of these techniques may lead to the development of autologous disc cell therapy comparable to that currently successfully used in hyaline cartilage defects of synovial joints in humans.

Purpose/introduction: 80% of individuals experience low back pain in their lifetime. This is often due to disc injury or degeneration. Conservative treatment of discogenic pain is often unsuccessful whilst surgery with the use of spacers of fusion is non-physiological. The aim of this study was to develop an animal model to assess the viability of autologous disc cell therapy.

Method: The Fat Sand Rat (Psammomys obesus obesus) was chosen due to its predisposition to the early development of spondylosis. Using microsurgical techniques fragments of annulus and nucleus were harvested from a single disc in 52 sand rats. Vascular clips were placed on the adjacent psoas muscle to mark the harvested level. Disc material was initially cultured in monolayer then transferred into a three dimensional culture media of agarose. This technique yields greater cellular proliferation and the development of cell growth in colonies. Cells were labelled with Bromodeoxyuridine for later immunohistochemical identification. 20 000 cells in a carrier media were then re-implanted at a second operation at an adjacent disc level in the same animal. The rat was subsequently euthanised and the histology of the disc space reviewed.

Results: To date 52 primary disc harvests and 20 reimplantations have been performed. 15 rats have been euthanised and sectioned. Average age at primary surgery was 6.8 months reimplantation eight months and euthanisation 11.2 months. Cell colony viability was inversely related to rat age at harvest. Immunohistochemical analysis of colony extracellular matrix revealed production of type 1 and 2 collagen, chondroitin and keratin sulphate Two rats died prior to reimplantation. All histological specimens confirm the presence of viable transplanted disc cells. Transplanted cells did not alter the progression of degenerative changes on x-ray.

Conclusion: Autologous disc cell transplantation can be performed in the rat. Further modification of these techniques may lead to the development of autologous disc cell therapy comparable to that currently successfully used in hyaline cartilage defects of synovial joints in humans.