Kajabadi Nasim-Sadat, Ghoochani Ali, Peymani Maryam, Ghaedi Kamran, Kiani-Esfahani Abbas, Hashemi Motahareh-Sadat, Nasr-Esfahani Mohammad Hossein, Baharvand Hossein
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.
J Biol Chem. 2015 Oct 23;290(43):26303-13. doi: 10.1074/jbc.M114.624841. Epub 2015 Sep 2.
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.
尽管人类多能干细胞（hPSC）为再生医学提供了宝贵的来源，但其适用性取决于获得合适的大规模培养且具有成本效益的培养物。Rho相关激酶（ROCK）抑制剂Y-27632可使hPSC在解离后存活；然而，克隆效率通常仍然很低。在这里，我们已经表明，吡格列酮，一种选择性过氧化物酶体增殖物激活受体-γ激动剂，与Y-27632协同作用，可减少解离诱导的细胞凋亡，并提高克隆效率（与Y-27632相比提高2-3倍），而不影响hPSC的多能性。吡格列酮通过抑制糖原合酶激酶（GSK3）活性以及增强膜性β-连环蛋白和E-钙黏蛋白发挥其积极作用。这些作用被GW-9662（一种不可逆的过氧化物酶体增殖物激活受体-γ拮抗剂）逆转。这种新方法为hPSC的操作及其生物医学应用迈出了一步。
