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利用CDMP1基因转染的自体骨髓间充质细胞修复兔关节软骨缺损

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

作者信息

Katayama R, Wakitani S, Tsumaki N, Morita Y, Matsushita I, Gejo R, Kimura T

机构信息

Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Japan.

出版信息

Rheumatology (Oxford). 2004 Aug;43(8):980-5. doi: 10.1093/rheumatology/keh240. Epub 2004 Jun 8.

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.

摘要

目的

软骨源性形态发生蛋白1(CDMP1)是转化生长因子-β超家族的成员,是间充质细胞聚集和软骨细胞分化加速所必需的分子。在本研究中,我们调查了转染CDMP1的自体骨髓间充质细胞(BMMCs)是否能增强兔模型中的体内软骨修复。

方法

从兔胫骨骨髓中分离出具有成纤维细胞形态和多能分化能力的BMMCs,在单层培养中生长,并用脂质转染法将CDMP1基因或对照基因(GFP)转染到细胞中。然后将自体细胞植入每只兔膝关节的全层关节软骨缺损处。

结果

在全层关节软骨缺损的体内修复过程中,转染CDMP1的自体BMMCs植入可增强软骨再生。缺损处被透明软骨填充,随着时间的推移,较深区域显示出向软骨下骨的重塑。透明关节软骨区域的修复和重建优于单纯BMMCs植入。转染CDMP1的BMMC组的组织学评分明显优于对照BMMC组和空白对照组。

结论

通过CDMP1等因子对BMMCs进行调节可增强与透明关节软骨相容的修复和重塑。

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