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Title: Hydrogen sulfide augments the proliferation and survival of human induced pluripotent stem cell-derived mesenchymal stromal cells through inhibition of BKCa
Authors: Zhao, Y.
Wei, H. 
Kong, G.
Shim, W. 
Zhang, G.
Keywords: Apoptosis
Human induced pluripotent stem cell-derived mesenchymal stromal cells
Large-conductance calcium-activated K+ channels
PI3K/Akt pathway
Issue Date: Nov-2013
Citation: Zhao, Y., Wei, H., Kong, G., Shim, W., Zhang, G. (2013-11). Hydrogen sulfide augments the proliferation and survival of human induced pluripotent stem cell-derived mesenchymal stromal cells through inhibition of BKCa. Cytotherapy 15 (11) : 1395-1405. ScholarBank@NUS Repository.
Abstract: Background: Hydrogen sulfide (H2S) is an endogenously generated gaseous transmitter known for its cytoprotective effect mediated by the PI3K-Akt signaling pathway. Human induced pluripotent stem cell (hiPSC)-derived mesenchymal stromal cells (MSCs), or hiPSC-MSCs, represent an alternative source of MSCs for autologous cell therapy. The big-conductance Ca2+-activated outward K+ currents (BKCa), known to mediate cell proliferation, have been detected in >80% of hiPSC-MSCs. The present study aimed to explore the effect of H2S on survival and proliferation of hiPSC-MSCs and investigate the mediatory role of BKCa. Methods: Effects of H2S on proliferation and survival of hiPSC-MSCs were measured by 5-bromo-2-deoxyuridine incorporation, population doubling and cell cycle assays, and by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide assay and 4'-6-diamidino-2-phenylindole staining, respectively. BKCa was recorded by means of the whole-cell patch-clamp technique. The expressions of KCa 1.1 (encoding BKCa) and apoptosis-related genes were measured by reverse transcriptase-polymerase chain reaction. The phosphorylation of Akt was assessed by Western blot analysis. Results: Exogenously administered NaHS (an H2S donor, 50-300 μmol/L) significantly promoted proliferation of hiPSC-MSCs. NaHS prevented the hypoxia-induced apoptosis and suppressed BKCa currents without altering the expression levels of α- and β-KCa 1.1. In addition, NaHS increased the phosphorylation of Akt and decreased the expression of Caspase 8 and Bax in hiPSC-MSCs. Paxilline (1μmol/L), a BKCa blocker, showed similar effects on promoting cell proliferation and phosphorylation of Akt and suppression of apoptotic genes in hiPSC-MSCs. Conclusions: Our data confirmed that H2S arguments the proliferation and survival of hiPSC-MSCs through activation of the PI3K-Akt pathway and that such effects could be mediated through inhibition ofBKCa. © 2013 International Society for Cellular Therapy.
Source Title: Cytotherapy
ISSN: 14653249
DOI: 10.1016/j.jcyt.2013.06.004
Appears in Collections:Staff Publications

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