期刊
STEM CELL REPORTS
卷 2, 期 3, 页码 271-281出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2014.01.011
关键词
-
资金
- [P01 HL094374]
- [R01 HL084642]
- [P01 GM081719]
- [U01 HL100405]
- [R01 HL64387]
- [T32 EB001650]
For cell-based treatments of myocardial infarction, a better understanding of key developmental signaling pathways and more robust techniques for producing cardiomyocytes are required. Manipulation of Notch signaling has promise as it plays an important role during cardiovascular development, but previous studies presented conflicting results that Notch activation both positively and negatively regulates cardiogenesis. We developed surface-and microparticle-based Notch-signaling biomaterials that function in a time-specific activation- tunable manner, enabling precise investigation of Notch activation at specific developmental stages. Using our technologies, a biphasic effect of Notch activation on cardiac differentiation was found: early activation in undifferentiated human embryonic stem cells (hESCs) promotes ectodermal differentiation, activation in specified cardiovascular progenitor cells increases cardiac differentiation. Signaling also induces cardiomyocyte proliferation, and repeated doses of Notch-signaling microparticles further enhance cardiomyocyte population size. These results highlight the diverse effects of Notch activation during cardiac development and provide approaches for generating large quantities of cardiomyocytes.
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