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Rheumatology Advance Access published online on June 8, 2004
Rheumatology, doi:10.1093/rheumatology/keh240
Rheumatology © British Society for Rheumatology 2004; all rights reserved
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Received November 4, 2003
Accepted April 19, 2004

Original Papers

Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow

R. Katayama 1, S. Wakitani 2, N. Tsumaki 3, Y. Morita 1, I. Matsushita 1, R. Gejo 1, T. Kimura 1*

1 Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Toyama, Japan
2 Department of Orthopaedic Surgery, Shinsyu University, Nagano, Japan
3 Department of Orthopaedic Surgery, Faculty of Medicine, Osaka University, Osaka, Japan

* To whom correspondence should be addressed. E-mail: tkimura{at}ms.toyama-mpu.ac.jp.


  Abstract

Objective. Cartilage-derived morphogenetic protein 1 (CDMP1), which is a member of the transforming growth factor-{beta} superfamily, is an essential molecule for the aggregation of mesenchymal cells and acceleration of chondrocyte differentiation. In this study, we investigated whether CDMP1-transfected autologous bone marrow-derived mesenchymal cells (BMMCs) enhance in vivo cartilage repair in a rabbit model.

Methods. BMMCs, which had a fibroblastic morphology and pluripotency for differentiation, were isolated from bone marrow of the tibia of rabbits, grown in monolayer culture, and transfected with the CDMP1 gene or a control gene (GFP) by the lipofection method. The autologous cells were then implanted into full-thickness articular cartilage defects in the knee joints of each rabbit.

Results. During in vivo repair of full-thickness articular cartilage defects, cartilage regeneration was enhanced by the implantation of CDMP1-transfected autologous BMMCs. The defects were filled by hyaline cartilage and the deeper zone showed remodelling to subchondral bone over time. The repair and reconstitution of zones of hyaline articular cartilage was superior to simple BMMC implantation. The histological score of the CDMP1-transfected BMMC group was significantly better than those of the control BMMC group and the empty control group.

Conclusion. Modulation of BMMCs by factors such as CDMP1 allows enhanced repair and remodelling compatible with hyaline articular cartilage.

KEY WORDS: Cartilage repair, Mesenchymal cell, Chondrogenic differentiation, CDMP1.


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