Abstract
Embryonic stem (ES) cells may be used as an alternative source of functionally intact cardiomyocytes for ischemic heart disease. Several natural and synthetic small molecules have been identified as useful tools for controlling and manipulating stem cell renewal and differentiation. Currently, there is an urgent requirement for novel small molecules that specifically induce differentiation of stem cells into cardiomyocytes. To identify compounds that promote cardiomyogenesis of stem cells, cell-based screening of a peptidomimetic small-molecule library was carried out. A series of β-turn peptidomimetic compounds, including CW209E, increased the expression of α-MHC promoter-driven enhanced green fluorescent protein (EGFP) and ratio of beating embryoid bodies (EBs) without inducing cytotoxicity in mouse embryonic stem cells. CW209E also increased the number of beating EBs in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Thus, this chemical compound should be useful for elucidation of the molecular pathway of cardiogenesis and generation of cardiomyocytes ex vivo, which can be further applied for experimental or clinical cell therapy for ischemic heart diseases.
Original language | English |
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Pages (from-to) | 1979-1988 |
Number of pages | 10 |
Journal | Archives of Pharmacal Research |
Volume | 35 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2012 |
Bibliographical note
Funding Information:Authors are grateful to Kyoung Baek for the ALP assay, and Dr. Masa Eguchi and Dr. Kathy Emami for critical review of the manuscript. This work was supported by the Research Program for NRL (R0A-2007-000-20016-0), New Drug Target Discovery (M1074800306-08N4800) grant from the Ministry of Education, Science & Technology, Korea, and JW Pharmaceutical Corp.
Keywords
- Cardiogenesis
- Embryonic stem cells
- Ischemic heart disease
- Peptidomimetic compounds