Gene & Stem Cell Therapy Program, Centenary Institute, Camperdown, New South Wales, Australia.
Nat Biotechnol. 2010 Oct;28(10):1123-8. doi: 10.1038/nbt.1687. Epub 2010 Oct 3.
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.
关于物理微环境对造血干细胞和祖细胞的影响,人们知之甚少。为了探究基质弹性对经过充分鉴定的原始造血细胞的物理影响,我们利用了一种独特的弹性生物材料——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,可使未分化细胞(包括祖细胞和小鼠干细胞)扩增两倍至三倍。在存在原弹性蛋白的情况下,细胞因子的处理对这种扩增具有附加效应。这种生物学效应需要基质的弹性,因为截短的或交联的原弹性蛋白都不能再现这种现象,并且机械转导的抑制消除了这种效应。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,可被用来促进细胞培养。