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利用转化生长因子-β1基因激活支架中的间充质干细胞改善软骨再生。

Improved cartilage regeneration utilizing mesenchymal stem cells in TGF-beta1 gene-activated scaffolds.

作者信息

Diao Huajia, Wang Jinliang, Shen Chao, Xia Suhua, Guo Ting, Dong Lei, Zhang Chenyu, Chen Jiangning, Zhao Jianning, Zhang Junfeng

机构信息

Department of Orthopaedics Surgery, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Jinling Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, China.

出版信息

Tissue Eng Part A. 2009 Sep;15(9):2687-98. doi: 10.1089/ten.TEA.2008.0621.

Abstract

Recently, bone marrow-derived mesenchymal stem cells (MSCs) have been paid more attention for cartilage regeneration. This study evaluated the potential of using MSCs seeded in plasmid transforming growth factor beta1 (pTGF-beta1)-activated three-dimensional chitosan/gelatin scaffolds for improving cartilage repair in vivo. Significant cell proliferation and transforming growth factor beta1 protein expression were observed in vitro in pTGFbeta1-activated scaffolds. Transforming growth factor beta1-activated scaffolds showed high collagen type II and aggrecan expression and low collagen type I expression during in vitro cultivation. MSC-based pTGF-beta1-activated scaffolds also exhibited cartilage histology with high secretion of collagen type II in vitro under the stimulation of pTGF-beta1. In rabbits with full-thickness cartilage defects, the implantation of MSC-based pTGF-beta1-activated scaffolds not only significantly promoted chondrogenic differentiation of MSCs and hyalin-like cartilage matrix synthesis, but also remarkably improved the overall repair of rabbit cartilage defects and exhibited favorable tissue integrity at 10 weeks postsurgery. These results suggest that MSC-based localized pTGF-beta1-activated scaffolds have potential applications for in vivo cartilage repair.

摘要

最近,骨髓间充质干细胞(MSCs)在软骨再生方面受到了更多关注。本研究评估了将MSCs接种于质粒转化生长因子β1(pTGF-β1)激活的三维壳聚糖/明胶支架中用于改善体内软骨修复的潜力。在体外,pTGF-β1激活的支架中观察到显著的细胞增殖和转化生长因子β1蛋白表达。在体外培养过程中,pTGF-β1激活的支架显示出高II型胶原蛋白和聚集蛋白聚糖表达以及低I型胶原蛋白表达。基于MSCs的pTGF-β1激活支架在pTGF-β1刺激下在体外也表现出具有高II型胶原蛋白分泌的软骨组织学特征。在全层软骨缺损的兔子中,植入基于MSCs的pTGF-β1激活支架不仅显著促进了MSCs的软骨分化和透明样软骨基质合成,而且在术后10周显著改善了兔子软骨缺损的整体修复,并表现出良好的组织完整性。这些结果表明,基于MSCs的局部pTGF-β1激活支架在体内软骨修复方面具有潜在应用价值。

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