Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects.
OBJECTIVE
To evaluate the effectiveness of transplanted allogeneic muscle derived cells (MDC) embedded in collagen gels for the treatment of full thickness articular cartilage defects, to compare the results to those from chondrocyte transplantation, and to evaluate the feasibility of MDC based ex vivo gene therapy for cartilage repair.


METHODS
Rabbit MDC and chondrocytes were transduced with a retrovirus encoding for the beta-galactosidase gene (LacZ). The cells were embedded in type I collagen gels, and the cell proliferation and transgene expression were investigated in vitro. In vivo, collagen gels containing transduced cells were grafted to the experimental full thickness osteochondral defects. The repaired tissues were evaluated histologically and histochemically, and collagen typing of the tissue was performed.


RESULTS
The MDC and chondrocyte cell numbers at 4 weeks of culture were 305 +/- 25% and 199 +/- 25% of the initial cell number, respectively. The initial percentages of LacZ positive cells in the MDC and chondrocyte groups were 95.4 +/- 1.9% and 93.4 +/- 3.4%, and after 4 weeks of culture they were 84.2 +/- 3.9% and 76.9 +/- 4.3%, respectively. In vivo, although grafted cells were found in the defects only up to 4 weeks after transplantation, the repaired tissues in the MDC and chondrocyte groups were similarly better histologically than control groups. Repaired tissues in the MDC group were mainly composed of type II collagen, as in the chondrocyte group.


CONCLUSIONS
Allogeneic MDC could be used for full thickness articular cartilage repair as both a gene delivery vehicle and a cell source for tissue repair.
Adachi
Nobuo
N
Department of Orthopaedic Surgery, Children's Hospital of Pittsburgh, and University of Pittsburgh, Pennsylvania 15213, USA.
Sato
Kenji
K
Usas
Arvydas
A
Fu
Freddie H
FH
Ochi
Mitsuo
M
Han
Chang-Whan
CW
Niyibizi
Christopher
C
Huard
Johnny
J
D000704:Analysis of Variance; D000818:Animals; D002357:Cartilage Diseases / Q000473:pathology / Q000628:therapy*; D002358:Cartilage, Articular / Q000293:injuries* / Q000473:pathology; D017690:Cell Transplantation; D019902:Chondrocytes / Q000637:transplantation*; D046508:Culture Techniques; D004195:Disease Models, Animal; D005260:Female; D005782:Gels; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D011336:Probability; D011817:Rabbits; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D005782:Gels