StemBond hydrogels optimise the mechanical microenvironment for embryonic stem cells

StemBond hydrogels optimise the mechanical microenvironment for embryonic stem cells
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StemBond 水凝胶优化胚胎干细胞的机械微环境

DOI:
10.1101/768762
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发表时间:
2019
期刊:
--
影响因子:
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通讯作者:
Labouesse C
Labouesse C
中科院分区:
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作者:
Labouesse C

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机械信号的研究通常是通过比较在软性和硬性水凝胶基质上培养的细胞来进行的。然而,独立且稳健地控制底物刚度和细胞外基质(ECM)与底物的捆绑是一项挑战,这使得ECM捆绑在机械信号研究中成为一个潜在的混淆变量。此外,较差的ECM栓系会导致细胞附着较弱。为了解决这个问题,我们开发了StemBond水凝胶,这是一种水凝胶配方,其中ECM系索稳定,可以独立于刚度变化。我们表明,软StemBond水凝胶为培养胚胎干细胞(ES)提供了最佳格式。我们发现,软StemBond底物改善了胚胎干细胞群体的均匀性,促进了它们的自我更新,并提高了细胞重编程的效率。我们的研究结果强调了软微环境如何影响调节自我更新和分化的机械敏感信号通路,表明优化完整的机械微环境将提供对干细胞命运规范的更大控制。
Studies of mechanical signalling are typically performed by comparing cells cultured on soft and stiff hydrogel-based substrates. However, it is challenging to independently and robustly control both substrate stiffness and tethering of extracellular matrix (ECM) to substrates, making ECM tethering a potentially confounding variable in mechanical signalling investigations. Moreover, poor ECM tethering can lead to weak cell attachment. To address this, we developed StemBond hydrogels, a hydrogel formulation in which ECM tethering is stable and can be varied independently of stiffness. We show that soft StemBond hydrogels provide an optimal format for culturing embryonic stem (ES) cells. We find that soft StemBond substrates improve the homogeneity of ES cell populations, boost their self-renewal, and increase the efficiency of cellular reprogramming. Our findings underline how soft microenvironments impact mechanosensitive signalling pathways regulating self-renewal and differentiation, indicating that optimising the complete mechanical microenvironment will offer greater control over stem cell fate specification.
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