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The effect of co-culturing costal chondrocytes and dental pulp stem cells combined with exogenous FGF9 protein on chondrogenesis and ossification in engineered cartilage

机译:共同培养肋软骨细胞和牙髓干细胞与外源性FGF9蛋白联合对工程软骨软骨形成和骨化的影响

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摘要

Dental pulp stem cells (DPSCs), which arise from cranial neural crest cells, are multipotent, making them a candidate for use in tissue engineering that may be especially useful for craniofacial tissues. Costal chondrocytes (CCs) can be easily obtained and demonstrate higher initial cell yields and expansion than articular chondrocytes. CCs have been found to retain chondrogenic capacity that can effectively repair articular defects. In this study, human CCs were co-cultured with human DPSCs, and the results showed that the CCs were able to supply a chondro-inductive niche that promoted the DPSCs to undergo chondrogenic differentiation and to enhance the formation of cartilage. Although CCs alone could not prevent the mineralization of chondro-differentiated DPSCs, CCs combined with exogenous FGF9 were able to simultaneously promote the chondrogenesis of DPSCs and partially inhibit their mineralization. Furthermore, FGF9 may activate this inhibition by binding to FGFR3 and enhancing the phosphorylation of ERK1/2 in DPSCs. Our results strongly suggest that the co-culture of CCs and DPSCs combined with exogenous FGF9 can simultaneously enhance chondrogenesis and partially inhibit ossification in engineered cartilage.
机译:来自颅神经c细胞的牙髓干细胞(DPSC)具有多能性,使其成为组织工程中可能特别适用于颅面组织的候选对象。肋软骨细胞(CCs)可以轻松获得,并且比关节软骨细胞具有更高的初始细胞产量和扩增能力。已经发现CC保留了可以有效修复关节缺损的软骨形成能力。在这项研究中,人类CC与人类DPSC共同培养,结果表明CC能够提供软骨诱导的利基,促进DPSC经历软骨分化,并增强软骨的形成。尽管仅CCs不能阻止软骨分化的DPSC的矿化,但CCs与外源性FGF9结合能够同时促进DPSC的软骨形成并部分抑制其矿化。此外,FGF9可以通过与FGFR3结合并增强DPSC中ERK1 / 2的磷酸化来激活这种抑制作用。我们的结果强烈表明,CC和DPSC与外源性FGF9的共培养可同时增强软骨生成并部分抑制工程软骨的骨化。

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