Peptidomimetic small-molecule compounds promoting cardiogenesis of stem cells

Se Woong Oh; Jung Bok Lee; Bora Kim; Sejin Jeon; Min Kyoung Kim; Ki Hoan Nam; Jong Ryul Ha; Mickie Bhatia; Goo Taeg Oh; Dae Yong Kim

doi:10.1007/s12272-012-1115-6

Peptidomimetic small-molecule compounds promoting cardiogenesis of stem cells

Se Woong Oh, Jung Bok Lee, Bora Kim, Sejin Jeon, Min Kyoung Kim, Ki Hoan Nam, Jong Ryul Ha, Mickie Bhatia, Goo Taeg Oh, Dae Yong Kim

Life Sciences

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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
Pages (from-to)	1979-1988
Number of pages	10
Journal	Archives of Pharmacal Research
Volume	35
Issue number	11
DOIs	https://doi.org/10.1007/s12272-012-1115-6
State	Published - Nov 2012

Keywords

Cardiogenesis
Embryonic stem cells
Ischemic heart disease
Peptidomimetic compounds

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10.1007/s12272-012-1115-6

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title = "Peptidomimetic small-molecule compounds promoting cardiogenesis of stem cells",

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.",

keywords = "Cardiogenesis, Embryonic stem cells, Ischemic heart disease, Peptidomimetic compounds",

author = "Oh, {Se Woong} and Lee, {Jung Bok} and Bora Kim and Sejin Jeon and Kim, {Min Kyoung} and Nam, {Ki Hoan} and Ha, {Jong Ryul} and Mickie Bhatia and Oh, {Goo Taeg} and Kim, {Dae Yong}",

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.",

year = "2012",

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doi = "10.1007/s12272-012-1115-6",

language = "English",

volume = "35",

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AU - Oh, Se Woong

AU - Lee, Jung Bok

AU - Kim, Bora

AU - Jeon, Sejin

AU - Kim, Min Kyoung

AU - Nam, Ki Hoan

AU - Ha, Jong Ryul

AU - Bhatia, Mickie

AU - Oh, Goo Taeg

AU - Kim, Dae Yong

N1 - 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.

PY - 2012/11

Y1 - 2012/11

N2 - 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.

AB - 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.

KW - Cardiogenesis

KW - Embryonic stem cells

KW - Ischemic heart disease

KW - Peptidomimetic compounds

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JF - Archives of Pharmacal Research

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ER -

Peptidomimetic small-molecule compounds promoting cardiogenesis of stem cells

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