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Crosstalk between adipose-derived stem cells and chondrocytes: when growth factors matter

机译:脂肪干细胞与软骨细胞之间的串扰:当生长因子很重要时

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摘要

Adipose-derived stem cells (ASCs) and mesenchymal stem cells are promising for tissue repair because of their multilineage differentiation capacity. Our previous data confirmed that the implantation of mixed ASCs and chondrocytes into cartilage defects induced desirable in vivo healing outcomes. However, the paracrine action of ASCs on chondrocytes needs to be further elucidated. In this study, we established a co-culture system to achieve cell-to-cell and cell-to-tissue crosstalk and explored the soluble growth factors in both ASCs and chondrocytes supplemented with 1% fetal bovine serum to mimic the physiological microenvironment. In ASCs, we screened for growth factors by semi-quantitative PCR and quantitative real-time PCR and found that the expression of bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor B (VEGFB), hypoxia inducible factor-1α (HIF-1α), fibroblast growth factor-2 (FGF-2), and transforming growth factor-β1 significantly increased after co-culture in comparison with mono-culture. In chondrocytes, VEGFA was significantly enhanced after co-culture. Unexpectedly, the expression of collagen II and aggrecan was significantly down-regulated in the co-culture group compared with the mono-culture group. Meanwhile, among all the growth factors screened, we found that the BMP family members BMP-2, BMP-4, and BMP-5 were down-regulated and that VEGFB, HIF-1α, FGF-2, and PDGF were significantly decreased after co-culture. These results suggest that crosstalk between ASCs and chondrocytes is a pathway through the regulated growth factors that might have potential in cartilage repair and regeneration and could be useful for tissue engineering.
机译:脂肪干细胞(ASCs)和间充质干细胞由于其多系分化能力而有望用于组织修复。我们以前的数据证实,将混合的ASC和软骨细胞植入软骨缺损可诱导理想的体内愈合结果。但是,ASCs对软骨细胞的旁分泌作用需要进一步阐明。在这项研究中,我们建立了共培养系统以实现细胞间和细胞间的串扰,并探索了补充了1%胎牛血清以模拟生理微环境的ASC和软骨细胞中的可溶性生长因子。在ASC中,我们通过半定量PCR和实时定量PCR筛选了生长因子,发现骨形态发生蛋白2(BMP-2),血管内皮生长因子B(VEGFB),低氧诱导因子-1α(与单一培养相比,共培养后,HIF-1α),成纤维细胞生长因子2(FGF-2)和转化生长因子β1显着增加。共培养后,在软骨细胞中,VEGFA显着增强。出乎意料的是,与单培养组相比,共培养组的胶原蛋白II和聚集蛋白聚糖的表达显着下调。同时,在筛选的所有生长因子中,我们发现BMP家族成员BMP-2,BMP-4和BMP-5被下调,而VEGFB,HIF-1α,FGF-2和PDGF显着降低。共培养。这些结果表明,ASC和软骨细胞之间的串扰是通过调节生长因子的途径,该生长因子可能在软骨修复和再生中具有潜力,并且可能对组织工程有用。

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