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Muscle Derived, Cell Based Ex Vivo Gene Therapy for Treatment of Full Thickness Articular Cartilage Defects
NOBUO ADACHI, KENJI SATO, ARVYDAS USAS, FREDDIE H. FU, MITSUO OCHI, CHANG-WHAN HAN, CHRISTOPHER NIYIBIZI, and JOHNNY HUARD
ABSTRACT.
Methods. Rabbit MDC and chondrocytes were transduced with a retrovirus encoding for the ß-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. Conclusion. Allogeneic MDC could be used for full thickness articular cartilage repair as both a gene delivery vehicle and a cell source for tissue repair. (J Rheumatol 2002;29:1920-30) Key Indexing Terms:
CARTILAGE
From the Growth and Development Laboratory, Department of Orthopaedic Surgery, Children's Hospital of Pittsburgh, and University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Supported by The Orris C. Hirtzel and Beatrice Dewey Hirtzel Memorial Foundation and the William F. and Jean W. Donaldson Chair at Children's Hospital of Pittsburgh. N. Adachi, MD; K. Sato, MD, PhD; A. Usas, MD; C-W. Han, MD, Growth and Development Laboratory, Department of Orthopaedic Surgery, Children's Hospital of Pittsburgh; C. Niyibizi, PhD, Ferguson Laboratory, Collagen Biochemistry Laboratory, Musculoskeletal Research Center; F.H. Fu, MD, DSc(Hon), Professor and Chair, Department of Orthopaedic Surgery, Division of Sports Medicine; J. Huard, PhD, Associate Professor, Department of Orthopaedic Surgery, Molecular Genetics and Biochemistry and Bioengineering, University of Pittsburgh; M. Ochi, MD, PhD, Professor, Department of Orthopaedic Surgery, Shimane Medical University, Izumo City, Shimane, Japan. Address reprint requests to Dr. J. Huard, Growth and Development Laboratory, Children's Hospital of Pittsburgh, 4151 Rangos Research Center, 3705 Fifth Avenue, Pittsburgh, PA 15213. E-mail: jhuard+@pitt.edu Submitted May 17, 2001; revision accepted March 20, 2002.
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