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间充质干细胞在凝胶状生物材料中的体内外软骨生成

Chondrogenesis of mesenchymal stem cells in gel-like biomaterials in vitro and in vivo.

作者信息

Dickhut Andrea, Gottwald Eric, Steck Eric, Heisel Christian, Richter Wiltrud

机构信息

Division of Experimental Orthopaedics, Orthopaedic University Hospital, Heidelberg, Germany.

出版信息

Front Biosci. 2008 May 1;13:4517-28. doi: 10.2741/3020.

Abstract

Gel-like carrier materials were introduced into cell therapy of cartilage lesions to improve chondrocyte retention and distribution in the defect. Mesenchymal stem cells (MSC) are now discussed as an alternative cell source for repair. We here asked whether distinct gel-like carriers can support chondrogenesis of MSC in vitro and lead to stable cartilage-like transplants in vivo. Chondrogenesis of MSC embedded in collagen type I gel, fibrin glue, Matrigel and PuraMatrix peptide hydrogel was assessed and gene expression analysis, proteoglycan content, and collagen synthesis were quantified. Differentiated constructs were transplanted subcutaneously into SCID mice. All carriers supported chondrogenesis in vitro, but displayed material-dependent differences on COL2A1 gene expression, total collagen synthesis and proteoglycan deposition. The undesired calcification and microossicle formation in ectopic transplants in vivo was consistently suppressed by Matrigel. In sum, gel-like biomaterials were suitable carriers for MSC and promoted chondrogenesis. Suppression of calcification by particular gel-like materials makes their use even more attractive for MSC-based tissue engineering approaches in cartilage repair.

摘要

凝胶状载体材料被引入软骨损伤的细胞治疗中,以改善软骨细胞在缺损处的保留和分布。间充质干细胞(MSC)现在被视为一种替代性的修复细胞来源。我们在此研究了不同的凝胶状载体是否能在体外支持MSC的软骨形成,并在体内形成稳定的类软骨移植体。评估了嵌入I型胶原凝胶、纤维蛋白胶、基质胶和PuraMatrix肽水凝胶中的MSC的软骨形成情况,并对基因表达分析、蛋白聚糖含量和胶原蛋白合成进行了定量。将分化后的构建体皮下移植到SCID小鼠体内。所有载体在体外均支持软骨形成,但在COL2A1基因表达、总胶原蛋白合成和蛋白聚糖沉积方面表现出材料依赖性差异。基质胶持续抑制了体内异位移植中不期望的钙化和微骨形成。总之,凝胶状生物材料是MSC的合适载体,并促进软骨形成。特定凝胶状材料对钙化的抑制作用使其在基于MSC的软骨修复组织工程方法中更具吸引力。

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