Department of Chemistry, City University of Hong Kong, Hong Kong, Hong Kong.
Melbourne Center for Nanofabrication, Victorian Node of the Australian National Fabrication, Clayton, Australia.
Tissue Eng Part B Rev. 2020 Dec;26(6):540-554. doi: 10.1089/ten.TEB.2020.0044. Epub 2020 May 5.
One of the most crucial components of regenerative medicine is the controlled differentiation of embryonic or adult stem cells into the desired cell lineage. Although most of the reported protocols of stem cell differentiation involve the use of soluble growth factors, it is increasingly evident that stem cells also undergo differentiation when cultured in the appropriate microenvironment. When cultured in decellularized tissues, for instance, stem cells can recapitulate the morphogenesis and functional specialization of differentiated cell types with speed and efficiency that often surpass the traditional growth factor-driven protocols. This suggests that the tissue microenvironment (TME) provides stem cells with a holistic "instructive niche" that harbors signals for cellular reprogramming. The translation of this into medical applications requires the decoding of these signals, but this has been hampered by the complexity of TME. This problem is often addressed by a reductionist approach, in which cells are exposed to substrates decorated with simple, empirically designed geometries, textures, and chemical compositions ("bottom-up" approach). Although these studies are invaluable in revealing the basic principles of mechanotransduction mechanisms, their physiological relevance is often uncertain. This review examines the recent progress of an alternative, "top-down" approach, in which the TME is treated as a holistic biological entity. This approach is made possible by recent advances in systems biology and fabrication technologies that enable the isolation, characterization, and reconstitution of TME. It is hoped that these new techniques will elucidate the nature of niche signals so that they can be extracted, replicated, and controlled. This review summarizes these emerging techniques and how the data they generated are changing our view on TME. Impact statement This review summarizes the current state of art of the understanding of instructive niche in the field of tissue microenvironment. Not only did we survey the use of different biochemical preparations as stimuli of stem cell differentiation and summarize the recent effort in dissecting the biochemical composition of these preparations, through the application of extracellular matrix (ECM) arrays and proteomics, but we also introduce the use of open-source, high-content immunohistochemistry projects in contributing to the understanding of tissue-specific composition of ECM. We believe this review would be highly useful for our peer researching in the same field. "Mr. Tulkinghorn is always the same… so oddly out of place and yet so perfectly at home." -Charles Dickens, .
再生医学中最关键的组成部分之一是将胚胎或成体干细胞受控分化为所需的细胞谱系。尽管大多数报道的干细胞分化方案都涉及使用可溶性生长因子，但越来越明显的是，当干细胞在适当的微环境中培养时，它们也会经历分化。例如，当在去细胞组织中培养时，干细胞可以快速有效地再现分化细胞类型的形态发生和功能特化，其速度和效率常常超过传统的生长因子驱动的方案。这表明组织微环境 (TME) 为干细胞提供了一个整体的“指令性小生境”，其中包含用于细胞重编程的信号。将这一点转化为医学应用需要解码这些信号，但由于 TME 的复杂性，这一直受到阻碍。这个问题通常通过还原论方法来解决，其中细胞暴露于用简单的、经验设计的几何形状、纹理和化学成分修饰的底物上（“自下而上”方法）。尽管这些研究对于揭示机械转导机制的基本原理非常有价值，但它们的生理相关性往往不确定。本文综述了一种替代的“自上而下”方法的最新进展，该方法将 TME 视为一个整体的生物实体。这种方法得益于系统生物学和制造技术的最新进展，这些技术使 TME 的分离、表征和重建成为可能。希望这些新技术能够阐明小生境信号的性质，以便能够提取、复制和控制它们。本文综述了这些新兴技术，以及它们产生的数据如何改变我们对 TME 的看法。 影响声明 本文综述了组织微环境领域中对指令性小生境理解的最新进展。我们不仅调查了不同生化制剂作为干细胞分化刺激物的应用，并通过细胞外基质 (ECM) 阵列和蛋白质组学总结了最近剖析这些制剂生化组成的努力，而且还介绍了开源、高内涵免疫组织化学项目在帮助理解 ECM 的组织特异性组成方面的应用。我们相信，这篇综述对我们同领域的同行会非常有用。 “图尔金霍恩先生总是一成不变……如此奇怪地格格不入，却又如此完美地自在。”——查尔斯·狄更斯，《荒凉山庄》
