TGF-β3-induced chondrogenesis in co-cultures of chondrocytes and mesenchymal stem cells on biodegradable scaffolds.

TGF-β3-induced chondrogenesis in co-cultures of chondrocytes and mesenchymal stem cells on biodegradable scaffolds.
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DOI:
10.1016/j.biomaterials.2013.09.086
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发表时间:
2014-01
期刊:
影响因子:
14
通讯作者:
Mikos, Antonios G.
Mikos, Antonios G.
中科院分区:
工程技术1区
文献类型:
--
作者:
Dahlin, Rebecca L.;Ni, Mengwei;Meretoja, Ville V.;Kasper, F. Kurtis;Mikos, Antonios G.

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在这项工作中,假设关节软骨细胞(AC)和间充质干细胞(MSCs)共培养将表现出对软骨源性刺激(如转化生长因子-β3)的敏感性增强,并且与每种细胞类型的单一培养相比,需要降低转化生长因子-β3的浓度才能实现同等水平的软骨形成。进一步推测,与单一培养相比,去除培养液中的转化生长因子-β3后,AC/MSCs复合培养的软骨细胞表型更为稳定。通过在电纺聚(ε-己内酯)支架上以1:3的比例单独培养AC和MSCs来研究这些假说。用0、1、3或10 ng/ml的转化生长因子β-3培养两周,两周后去除生长因子补充剂,再培养两周。在2周和4周后检测细胞增殖、细胞外基质产生和软骨形成基因的表达。结果表明,与AC或MSCs单独培养相比,共培养的AC和MSCs需要更少的转化生长因子-β3的浓度和持续时间才能达到相同的软骨形成水平。因此,目前的工作暗示,软骨工程共培养的前景因其强大的表型和对转化生长因子-β3的高度敏感性而增强。
In this work, it was hypothesized that co-cultures of articular chondrocytes (ACs) and mesenchymal stem cells (MSCs) would exhibit enhanced sensitivity to chondrogenic stimuli, such as TGF-β3, and would require a reduced concentration of TGF-β3 to achieve an equivalent level of chondrogenesis compared to monocultures of each cell type. Furthermore, it was hypothesized that compared to monocultures, the chondrogenic phenotype of AC/MSC co-cultures would be more stable upon the removal of TGF-β3 from the culture medium. These hypotheses were investigated by culturing ACs and MSCs alone and in a 1:3 ratio on electrospun poly(ε-caprolactone) scaffolds. All cell populations were cultured for two weeks with 0, 1, 3, or 10 ng/ml of TGF-β3. After two weeks growth factor supplementation was removed, and the constructs were cultured for two additional weeks. Cell proliferation, extracellular matrix production, and chondrogenic gene expression were evaluated after two and four weeks. The results demonstrated that co-cultures of ACs and MSCs require a reduced concentration and duration of TGF-β3 exposure to achieve an equivalent level of chondrogenesis compared to AC or MSC monocultures. Thus, the present work implicates that the promise of co-cultures for cartilage engineering is enhanced by their robust phenotype and heightened sensitivity to TGF-β3.
与关节软骨细胞和间充质干细胞共培养的软骨发生增强。
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