Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc.
METHODS
Disc degeneration and osteoarthritis are diseases of the matrix. Chondrocytes that have been removed from damaged cartilaginous tissues maintain a capacity to proliferate, produce, and secrete matrix components, and respond to physical stimuli such as dynamic loading. A dog model was used to investigate the hypothesis that autologous disc chondrocytes can be used to repair damaged intervertebral disc.


OBJECTIVE
Given the capacity for the cells in vitro to produce matrix molecules that would be appropriate for disc chondrocytes, the focus of the experiment was to investigate whether the cells would continue to sustain metabolic function after transplantation.


BACKGROUND
No evidence for long-term integration exists for cell transplantation in species other than rats and rabbits. Furthermore, no controlled studies of 1-year duration have been published.


METHODS
Disc chondrocytes were harvested and expanded in culture under controlled and defined conditions, returned to the same animals from which they had been sampled (autologous transplantation) via percutaneous delivery. The animals were analyzed at specific times after transplantation by several methods to examine whether disc chondrocytes integrated with the surrounding tissue, produced the appropriate intervertebral disc extracellular matrix, and might provide a formative solution to disc repair.


RESULTS
In the context of degenerative changes in an injury model: (1) autologous disc chondrocytes were expanded in culture and returned to the disc by a minimally invasive procedure after 12 weeks; (2) disc chondrocytes remained viable after transplantation as shown by Bromodeoxyuridine incorporation and maintained a capacity for proliferation after transplantation as depicted by histology; (3) transplanted disc chondrocytes produced an extracellular matrix that displayed composition similar to normal intervertebral disc tissue. Positive evidence of proteoglycan content was supported by accepted histochemical staining techniques such as Safranin O-Fast Green; (4) both type II and type I collagens were demonstrated in the regenerated intervertebral disc matrix by immunohistochemistry after chondrocyte transplantation; and (5) when the disc heights were analyzed for variance according to treatment, a statistically significantcorrelation between transplanting cells and retention of disc height was achieved.


CONCLUSIONS
Autologous chondrocyte transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration.
Ganey
Timothy
T
Atlanta Medical Center, Atlanta, Georgia 30312, USA. Timothy.Ganey@tenethealth.com
Libera
Jeanette
J
Moos
Verena
V
Alasevic
Olivera
O
Fritsch
Karl-Gerd
KG
Meisel
Hans Joerg
HJ
Hutton
William C
WC
D000818:Animals; D001973:Bromodeoxyuridine / Q000032:analysis; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D004285:Dogs; D005260:Female; D024022:Fibrillar Collagens / Q000032:analysis; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000166:cytology / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging; D011859:Radiography; D013122:Spinal Diseases / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*
D024022:Fibrillar Collagens; D001973:Bromodeoxyuridine