Increasing the physical size and nucleation status of human pluripotent stem cell-derived ventricular cardiomyocytes by cell fusion.

Autor:	Kong CW; Stem Cell & Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. Electronic address: marcokong@hku.hk., Chen S; Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong., Geng L; Stem Cell & Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; Dr. Li Dak-Sum Centre, The University of Hong Kong, Hong Kong., Shum AM; Stem Cell & Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong., Sun D; Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong., Li RA; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; Dr. Li Dak-Sum Centre, The University of Hong Kong, Hong Kong; Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Sweden.
Jazyk:	angličtina
Zdroj:	Stem cell research [Stem Cell Res] 2017 Mar; Vol. 19, pp. 76-81. Date of Electronic Publication: 2017 Jan 06.
DOI:	10.1016/j.scr.2017.01.003
Abstrakt:	Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) provide an unlimited source of donor cells for potential cardiac regenerative therapies. However, hPSC-CMs are immature. For instance, hPSC-CMs are only 1/10 of the physical size of their adult counterparts; the majority are mono- rather than bi- or multi-nucleated, which is an evolutionary adaptive feature in metabolically active cells such as adult CMs. Here, we attempted to increase the physical size and nucleation status of hPSC-derived ventricular (V) cardiomyocytes (hPSC-VCMs) using chemically-induced cell fusion, and examined the subsequent functional effects. Polyethylene glycol (PEG) was employed to fuse a 1:1 mixture of lentiviral vectors LV-MLC2v-GFP- or -tdTomato-labeled hPSC-VCMs, such that hPSC-VCMs fused syncytia (FS) were identified as doubly GFP + /tdTomato + multi-nucleated cells. These microscopically-identified FS were doubled in size as gauged by their capacitance when compared to the control mononucleated hPSC-VCMs using patch-clamp analysis. Reduced automaticity or action potential (AP) firing rate and moderately prolonged AP duration were observed in FS from day 6 post-fusion induction. However, Ca 2+ handling, mitochondrial biogenesis and the extent of apoptosis were not significantly altered. We conclude that larger, multi-nucleated hPSC-VCMs FS can be created by chemically-induced cell fusion but global maturation requires additional triggering cues. (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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