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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.
Human induced pluripotent stem cell-derived mesenchymal stromal cells
Large-conductance calcium-activated K+ channels
|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. https://doi.org/10.1016/j.jcyt.2013.06.004||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||URI:||http://scholarbank.nus.edu.sg/handle/10635/124731||ISSN:||14653249||DOI:||10.1016/j.jcyt.2013.06.004|
|Appears in Collections:||Staff Publications|
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