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, Johnny Huard

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)1920-1930
Number of pages11
JournalJournal of Rheumatology
Volume29
Issue number9
StatePublished - Sep 1 2002

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Articular Cartilage
Genetic Therapy
Muscle Cells
Chondrocytes
Collagen
Gels
Therapeutics
Cell Count
Galactosidases
Tissue Transplantation
Histocompatibility Testing
Lac Operon
Collagen Type II
Retroviridae
Collagen Type I
Transgenes
Cartilage
Transplantation
Cell Proliferation
Rabbits

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Adachi, N., Sato, K., Usas, A., Fu, F. H., Ochi, M., Han, C. W., ... Huard, J. (2002). Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects. Journal of Rheumatology, 29(9), 1920-1930.
Adachi, Nobuo ; Sato, Kenji ; Usas, Arvydas ; Fu, Freddie H. ; Ochi, Mitsuo ; Han, Chang Whan ; Niyibizi, Christopher ; Huard, Johnny. / Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects. In: Journal of Rheumatology. 2002 ; Vol. 29, No. 9. pp. 1920-1930.
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abstract = "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 β-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.",
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Adachi, N, Sato, K, Usas, A, Fu, FH, Ochi, M, Han, CW, Niyibizi, C & Huard, J 2002, 'Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects', Journal of Rheumatology, vol. 29, no. 9, pp. 1920-1930.

Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects. / Adachi, Nobuo; Sato, Kenji; Usas, Arvydas; Fu, Freddie H.; Ochi, Mitsuo; Han, Chang Whan; Niyibizi, Christopher; Huard, Johnny.

In: Journal of Rheumatology, Vol. 29, No. 9, 01.09.2002, p. 1920-1930.

Research output: Contribution to journalArticle

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T1 - Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects

AU - Adachi, Nobuo

AU - Sato, Kenji

AU - Usas, Arvydas

AU - Fu, Freddie H.

AU - Ochi, Mitsuo

AU - Han, Chang Whan

AU - Niyibizi, Christopher

AU - Huard, Johnny

PY - 2002/9/1

Y1 - 2002/9/1

N2 - 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 β-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.

AB - 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 β-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.

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