On human pluripotent stem cell control: The rise of 3D bioengineering and mechanobiology.

On human pluripotent stem cell control: The rise of 3D bioengineering and mechanobiology.
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DOI:
10.1016/j.biomaterials.2015.01.078
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发表时间:
2015-06
期刊:
影响因子:
14
通讯作者:
Fu, Jianping
Fu, Jianping
中科院分区:
工程技术1区
文献类型:
--
作者:
Shao, Yue;Sang, Jianming;Fu, Jianping

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人类多能干细胞(human pluripotent stem cells,hPSC)是一种具有广阔应用前景的干细胞资源,可用于组织器官再生、发育和疾病的体外模拟。为了实现其承诺,hPSC的命运、功能和组织需要在三维(3D)环境中精确调节,以模拟天然组织和器官的细胞结构和功能。在过去的十年中,具有功能性生物材料的3D培养系统的创新使得能够在细胞水平上有效和多功能地控制hPSC的命运。然而,我们才刚刚开始将基于hPSC的再生和发育以及疾病建模带到组织和器官水平。在这篇综述中,我们总结了现有的生物工程培养平台控制hPSC的命运和功能,通过调节诱导机械和生化线索共存于合成细胞微环境。我们强调了最近在开发具有体内样细胞结构、相互作用和功能的基于3D hPSC的体外组织和器官模型方面的进展。我们进一步讨论了一个新兴的多方面的机械转导信号网络-转录辅激活因子雅普和TAZ在中心阶段-调节哺乳动物细胞,包括hPSC的命运和行为。3D生物材料系统的未来开发应结合动态调节的机械和化学性质,靶向特定的细胞内信号传导事件,从而在3D中形成所需的hPSC命运模式和功能组织。
Human pluripotent stem cells (hPSCs) provide promising resources for regenerating tissues and organs and modeling development and diseases in vitro. To fulfill their promise, the fate, function, and organization of hPSCs need to be precisely regulated in a three-dimensional (3D) environment to mimic cellular structures and functions of native tissues and organs. In the past decade, innovations in 3D culture systems with functional biomaterials have enabled efficient and versatile control of hPSC fate at the cellular level. However, we are just at the beginning of bringing hPSC-based regeneration and development and disease modeling to the tissue and organ levels. In this review, we summarize existing bioengineered culture platforms for controlling hPSC fate and function by regulating inductive mechanical and biochemical cues coexisting in the synthetic cell microenvironment. We highlight recent excitements in developing 3D hPSC-based in vitro tissue and organ models with in vivo-like cellular structures, interactions, and functions. We further discuss an emerging multifaceted mechanotransductive signaling network – with transcriptional coactivators YAP and TAZ at the center stage – that regulate fates and behaviors of mammalian cells, including hPSCs. Future development of 3D biomaterial systems should incorporate dynamically modulated mechanical and chemical properties targeting specific intracellular signaling events leading to desirable hPSC fate patterning and functional tissue formation in 3D.
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