期刊
STEM CELLS
卷 33, 期 7, 页码 2148-2157出版社
WILEY
DOI: 10.1002/stem.2036
关键词
Cardiac; Differentiation; Vascular development; Progenitor cells; Induced pluripotent stem cells; Embryonic stem cells; Cardiovascular progenitor; Cardiovascular tissue engineering
资金
- NIH [R01HL084642, R01HL111197, P01HL094374, U01HL100405, P01GM081619, T32HL007312, T32GM007266-MSTP]
Recent advances in pluripotent stem cell biology and directed differentiation have identified a population of human cardiovascular progenitors that give rise to cardiomyocytes, smooth muscle, and endothelial cells. Because the heart develops from progenitors in 3D under constant mechanical load, we sought to test the effects of a 3D microenvironment and mechanical stress on differentiation and maturation of human cardiovascular progenitors into myocardial tissue. Progenitors were derived from embryonic stem cells, cast into collagen hydrogels, and left unstressed or subjected to static or cyclic mechanical stress. Compared to 2D culture, the unstressed 3D environment increased cardiomyocyte numbers and decreased smooth muscle numbers. Additionally, 3D culture suppressed smooth muscle -actin content, suggesting diminished cell maturation. Cyclic stress-conditioning increased expression of several cardiac markers, including -myosin heavy chain and cardiac troponin T, and the tissue showed enhanced calcium dynamics and force production. There was no effect of mechanical loading on cardiomyocyte or smooth muscle specification. Thus, 3D growth conditions favor cardiac differentiation from cardiovascular progenitors, whereas 2D conditions promote smooth muscle differentiation. Mechanical loading promotes cardiomyocyte structural and functional maturation. Culture in 3-D facilitates understanding how cues such as mechanical stress affect the differentiation and morphogenesis of distinct cardiovascular cell populations into organized, functional human cardiovascular tissue. Stem Cells 2015;33:2148-2157
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据