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


CONCLUSIONS
Modulation of BMMCs by factors such as CDMP1 allows enhanced repair and remodelling compatible with hyaline articular cartilage.
Katayama
R
R
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Japan. riek@ms.toyama-mpu.ac.jp
Wakitani
S
S
Tsumaki
N
N
Morita
Y
Y
Matsushita
I
I
Gejo
R
R
Kimura
T
T
D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D016723:Bone Remodeling / Q000502:physiology; D002358:Cartilage, Articular / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology*; D003094:Collagen / Q000032:analysis; D055428:Growth Differentiation Factor 5; D006614:Hindlimb; D007150:Immunohistochemistry / Q000379:methods; D008648:Mesoderm / Q000502:physiology*; D011817:Rabbits; D014162:Transfection
D019485:Bone Morphogenetic Proteins; D055428:Growth Differentiation Factor 5; D003094:Collagen