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J Biol Chem. 2015 Oct 23;290(43):26303-13. doi: 10.1074/jbc.M114.624841. Epub 2015 Sep 2.

The Synergistic Enhancement of Cloning Efficiency in Individualized Human Pluripotent Stem Cells by Peroxisome Proliferative-activated Receptor-γ (PPARγ) Activation and Rho-associated Kinase (ROCK) Inhibition.

Author information

1
From the Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan 8174673441, Iran.
2
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan 8165131378, Iran.
3
From the Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan 8174673441, Iran, Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan 8165131378, Iran, kamranghaedi@royaninstitute.org.
4
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan 8165131378, Iran, mh_nasr@royaninstitute.org.
5
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran, and Baharvand@royaninstitute.org.

Abstract

Although human pluripotent stem cells (hPSCs) provide valuable sources for regenerative medicine, their applicability is dependent on obtaining both suitable up-scaled and cost effective cultures. The Rho-associated kinase (ROCK) inhibitor Y-27632 permits hPSC survival upon dissociation; however, cloning efficiency is often still low. Here we have shown that pioglitazone, a selective peroxisome proliferative-activated receptor-γ agonist, along with Y-27632 synergistically diminished dissociation-induced apoptosis and increased cloning efficiency (2-3-fold versus Y-27632) without affecting pluripotency of hPSCs. Pioglitazone exerted its positive effect by inhibition of glycogen synthase kinase (GSK3) activity and enhancement of membranous β-catenin and E-cadherin proteins. These effects were reversed by GW-9662, an irreversible peroxisome proliferative-activated receptor-γ antagonist. This novel setting provided a step toward hPSC manipulation and its biomedical applications.

KEYWORDS:

apoptosis; cell adhesion; embryonic stem cell; induced pluripotent stem cell (iPS cell) (iPSC); pioglitazone; signaling; β-catenin (B-catenin)

PMID:
26336103
PMCID:
PMC4646278
DOI:
10.1074/jbc.M114.624841
[Indexed for MEDLINE]
Free PMC Article

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