A home away from home: challenges and opportunities in engineering in vitro muscle satellite cell niches.
A home away from home: challenges and opportunities in engineering in vitro muscle satellite cell niches.
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DOI：
10.1016/j.diff.2009.08.004
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发表时间：
2009-09
期刊：
影响因子：
2.9
通讯作者：
Blau, Helen M.
中科院分区：
文献类型：
--
作者：
Cosgrove, Benjamin D.;Sacco, Alessandra;Gilbert, Penney M.;Blau, Helen M.
关键词：
卫星细胞是骨骼肌干细胞，在出生后骨骼肌再生中起主要作用。与许多组织特异性成体干细胞一样，卫星细胞在一个有指导意义的、解剖学上定义的生态位中处于静止状态。卫星细胞生态位构成肌纤维内独特的膜封闭室，包含影响卫星细胞功能的多种生化和生物物理信号。卫星细胞研究和临床应用的一个主要限制是，当从肌肉纤维中取出并在传统塑料组织培养平台中铺板时，它们的肌肉干细胞特性会迅速丧失。显然，干细胞功能的维持严重依赖于体内生态位信号，这突出表明需要创建新的体外微环境，以允许卫星细胞的维持和繁殖，同时保留其作为肌肉干细胞发挥功能的潜力。在这里，我们讨论新兴的生物材料技术如何为体外微环境工程带来巨大希望，以应对这些挑战。在工程生物材料中，信号分子可以以更接近地模拟细胞-细胞和细胞-基质相互作用的方式呈现，并且可以以接近体内组织的不同刚性来制造基质。可以系统地调节生态位特征的体外微环境的发展不仅有助于未来深入了解肌肉干细胞生物学以及肌肉疾病和衰老肌肉萎缩的治疗方法，而且还将为分析众多成体组织特异性干细胞提供范例。
Satellite cells are skeletal muscle stem cells with a principal role in postnatal skeletal muscle regeneration. Satellite cells, like many tissue-specific adult stem cells, reside in a quiescent state in an instructive, anatomically defined niche. The satellite cell niche constitutes a distinct membrane-enclosed compartment within the muscle fiber, containing a diversity of biochemical and biophysical signals that influence satellite cell function. A major limitation to the study and clinical utility of satellite cells is that upon removal from the muscle fiber and plating in traditional plastic tissue culture platforms, their muscle stem cell properties are rapidly lost. Clearly, the maintenance of stem cell function is critically dependent on in vivo niche signals, highlighting the need to create novel in vitro microenvironments that allow for the maintenance and propagation of satellite cells while retaining their potential to function as muscle stem cells. Here, we discuss how emerging biomaterials technologies offer great promise for engineering in vitro microenvironments to meet these challenges. In engineered biomaterials, signaling molecules can be presented in a manner that more closely mimics cell-cell and cell-matrix interactions and matrices can be fabricated with diverse rigidities that approximate in vivo tissues. The development of in vitro microenvironments in which niche features can be systematically modulated will be instrumental not only to future insights into muscle stem cell biology and therapeutic approaches to muscle diseases and muscle wasting with aging, but also will provide a paradigm for the analysis of numerous adult tissue-specific stem cells.
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