Biological Effects of Culture Substrates on Human Pluripotent Stem Cells.

Biological Effects of Culture Substrates on Human Pluripotent Stem Cells.
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DOI:
10.1155/2016/5380560
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发表时间:
2016
影响因子:
4.3
通讯作者:
Furue MK
Furue MK
中科院分区:
医学3区
文献类型:
--
作者:
Hayashi Y;Furue MK

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近年来,随着人多能干细胞(hPSC)普遍在无饲养层条件下培养,许多细胞培养基质已被应用或开发。然而,这些底物在维持 hPSC 自我更新中的功能作用仍不清楚。在这篇综述中,我们总结了这些底物的类型及其对维持 hPSC 自我更新的影响。内源性细胞外基质 (ECM) 蛋白表达已被证明对于维持 hPSC 自我更新至关重要。这些 ECM 分子与整合素细胞表面受体相互作用并传递其细胞信号。我们讨论了整合素介导的信号通路对维持 hPSC 自我更新的可能影响。整合素连接激酶 (ILK) 的激活可将 ECM 整合素信号传导至 AKT(也称为蛋白激酶 B),已被证明对于维持 hPSC 自我更新至关重要。此外,由于幼稚多能性已被广泛认为是 hPSC 的另一种多能状态,因此我们基于小鼠胚胎干细胞的研究,讨论了培养基质和整合素信号传导对幼稚 hPSC 的可能影响。了解培养基质在 hPSC 自我更新和分化中的作用使我们能够精确控制 hPSC 行为,并为再生医学和药物开发建立可扩展或微制造的培养技术。
In recent years, as human pluripotent stem cells (hPSCs) have been commonly cultured in feeder-free conditions, a number of cell culture substrates have been applied or developed. However, the functional roles of these substrates in maintaining hPSC self-renewal remain unclear. Here in this review, we summarize the types of these substrates and their effect on maintaining hPSC self-renewal. Endogenous extracellular matrix (ECM) protein expression has been shown to be crucial in maintaining hPSC self-renewal. These ECM molecules interact with integrin cell-surface receptors and transmit their cellular signaling. We discuss the possible effect of integrin-mediated signaling pathways on maintaining hPSC self-renewal. Activation of integrin-linked kinase (ILK), which transmits ECM-integrin signaling to AKT (also known as protein kinase B), has been shown to be critical in maintaining hPSC self-renewal. Also, since naïve pluripotency has been widely recognized as an alternative pluripotent state of hPSCs, we discuss the possible effects of culture substrates and integrin signaling on naïve hPSCs based on the studies of mouse embryonic stem cells. Understanding the role of culture substrates in hPSC self-renewal and differentiation enables us to control hPSC behavior precisely and to establish scalable or microfabricated culture technologies for regenerative medicine and drug development.
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