Substrate elasticity provides mechanical signals for the expansion of hemopoietic stem and progenitor cells
Substrate elasticity provides mechanical signals for the expansion of hemopoietic stem and progenitor cells
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DOI：
10.1038/nbt.1687
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发表时间：
2010-10-01
影响因子：
46.9
通讯作者：
Rasko, John E. J.
中科院分区：
文献类型：
--
作者：
Holst, Jeff;Watson, Sarah;Rasko, John E. J.
令人惊讶的是，人们对物理微环境对造血干细胞和祖细胞的影响知之甚少。为了探究基质弹性对特征明确的原始造血细胞的物理影响，我们利用了一种具有独特弹性的生物材料——原弹性蛋白。在原弹性蛋白基质上培养小鼠或人类造血细胞，导致未分化细胞（包括祖细胞和小鼠干细胞）扩增2到3倍。在原弹性蛋白存在的情况下用细胞因子处理对这种扩增有累加效应。这些生物学效应需要基质弹性，因为截短的或交联的原弹性蛋白都不能重现这一现象，并且抑制机械传导会消除这些效应。我们的数据表明，基质弹性和张力完整性是影响造血干细胞和祖细胞亚群的重要机制，可被利用来促进细胞培养。
Surprisingly little is known about the effects of the physical microenvironment on hemopoietic stem and progenitor cells. To explore the physical effects of matrix elasticity on well-characterized primitive hemopoietic cells, we made use of a uniquely elastic biomaterial, tropoelastin. Culturing mouse or human hemopoietic cells on a tropoelastin substrate led to a two- to threefold expansion of undifferentiated cells, including progenitors and mouse stem cells. Treatment with cytokines in the presence of tropoelastin had an additive effect on this expansion. These biological effects required substrate elasticity, as neither truncated nor cross-linked tropoelastin reproduced the phenomenon, and inhibition of mechanotransduction abrogated the effects. Our data suggest that substrate elasticity and tensegrity are important mechanisms influencing hemopoietic stem and progenitor cell subsets and could be exploited to facilitate cell culture.