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Soluble Collagen VI treatment enhances mesenchymal stem cells expansion for engineering cartilage

机译:可溶性VI胶原蛋白处理增强了间充质干细胞对工程软骨的扩增

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摘要

Bone Marrow‐derived mesenchymal stem cells (BM‐MSC) are an attractive source for cell‐based therapies in cartilage injury owing to their efficient differentiation into chondrocytes and their immune‐suppressive abilities. However, their clinical use is hampered by a scarcity of cells leading to compromised efficacy. While expansion of human MSC ex vivo can potentially overcome the scarcity of cells, current methods lead to a rapid loss of the stem cell properties. In this study, we report soluble Collagen VI (cartilage pericellular matrix component) as a potential biologic that can expand the MSC population while maintaining the stem cell phenotype as confirmed by expression of the stem cell markers CD105 and CD90. Short‐term treatment with Collagen VI additionally retains the potential of MSC to differentiate into mature chondrocytes in pellet culture. Cartilage pellets generated from MSC treated with Collagen VI or control express comparable amounts of the chondrogenic markers Collagen II, Aggrecan and Sox9, and the extracellular glycosaminoglycans. Our observations confirm that the use of the endogenous and cartilage‐specific factor Collagen VI is valuable for a rapid and efficient expansion of MSC for potential use in cartilage regeneration and osteoarthritis.
机译:骨髓间充质干细胞(BM-MSC)是软骨损伤中基于细胞的治疗方法的一种有吸引力的来源,因为它们能有效分化为软骨细胞并具有免疫抑制能力。但是,它们的临床使用受到细胞稀缺的阻碍,从而导致功效受损。虽然人MSC的离体扩增可以潜在地克服细胞的稀缺性,但当前的方法导致干细胞特性的快速丧失。在这项研究中,我们报告了可溶性胶原VI(作为细胞周围基质成分)作为一种潜在的生物学物质,可以扩展MSC群体,同时保持干细胞表型,这通过干细胞标记CD105和CD90的表达得以证实。胶原蛋白VI的短期治疗还保留了MSC在沉淀培养中分化为成熟软骨细胞的潜力。由胶原VI或对照处理过的MSC产生的软骨沉淀表达了相当数量的软骨生成标记胶原II,Aggrecan和Sox9,以及细胞外糖胺聚糖。我们的观察结果证实,内源性和软骨特异性因子胶原VI的使用对于快速有效地扩增MSC具有潜在价值,可用于软骨再生和骨关节炎。

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