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.
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.
From the Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan 8174673441, Iran.
Nasim-Sadat
NS
Kajabadi
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan 8165131378, Iran.
Ali
A
Ghoochani
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan 8165131378, Iran.
Maryam
M
Peymani
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.
Kamran
K
Ghaedi
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan 8165131378, Iran.
Abbas
A
Kiani-Esfahani
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan 8165131378, Iran.
Motahareh-Sadat
MS
Hashemi
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan 8165131378, Iran, mh_nasr@royaninstitute.org.
Mohammad Hossein
MH
Nasr-Esfahani
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.
Hossein
H
Baharvand
D000577:Amides / Q000494:pharmacology; D002999:Clone Cells; D006801:Humans; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000378:metabolism; D000077205:Pioglitazone; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000577:Amides; D047492:Peroxisome Proliferator-Activated Receptors; D011725:Pyridines; D045162:Thiazolidinediones; C108830:Y 27632; D054460:rho-Associated Kinases; D000077205:Pioglitazone
apoptosis; cell adhesion; embryonic stem cell; induced pluripotent stem cell (iPS cell) (iPSC); pioglitazone; signaling; β-catenin (B-catenin)