Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0103485
Title: A systemic evaluation of cardiac differentiation from mRNA reprogrammed human induced pluripotent stem cells
Authors: Mehta A. 
Verma V.
Nandihalli M.
Ramachandra C.J.A.
Sequiera G.L.
Sudibyo Y.
Chung Y.
Sun W. 
Shim W. 
Keywords: 1 [2 (6 methyl 2 pyridyl)ethyl] 4 (4 methylsulfonylaminobenzoyl)piperidine
adrenergic receptor
calcium channel
isoprenaline
messenger RNA
nifedipine
potassium channel
sodium channel
sodium ion
sotalol
tetrodotoxin
carbachol
cardiotonic agent
cholinergic receptor stimulating agent
ion channel
isoprenaline
messenger RNA
octamer transcription factor 4
stage specific embryo antigen
stage-specific embryonic antigen-4
adult
animal experiment
animal tissue
article
cell differentiation
controlled study
gene expression
heart
heart contraction
heart muscle cell
human
human cell
in vitro study
male
mesoderm
middle aged
mouse
nonhuman
nuclear reprogramming
pluripotent stem cell
QT prolongation
skin fibroblast
sodium transport
tissue differentiation
cell culture
cell reprogramming technique
confocal microscopy
cytology
drug effects
evaluation study
fibroblast
genetics
membrane potential
metabolism
nuclear reprogramming
physiology
pluripotent stem cell
procedures
reverse transcription polymerase chain reaction
Carbachol
Cardiotonic Agents
Cell Differentiation
Cells, Cultured
Cellular Reprogramming
Cellular Reprogramming Techniques
Cholinergic Agonists
Fibroblasts
Gene Expression
Humans
Induced Pluripotent Stem Cells
Ion Channels
Isoproterenol
Male
Membrane Potentials
Microscopy, Confocal
Middle Aged
Myocytes, Cardiac
Octamer Transcription Factor-3
Pluripotent Stem Cells
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger
Stage-Specific Embryonic Antigens
Issue Date: 2014
Citation: Mehta A., Verma V., Nandihalli M., Ramachandra C.J.A., Sequiera G.L., Sudibyo Y., Chung Y., Sun W., Shim W. (2014). A systemic evaluation of cardiac differentiation from mRNA reprogrammed human induced pluripotent stem cells. PLoS ONE 9 (7) : e103485. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0103485
Abstract: Genetically unmodified cardiomyocytes mandated for cardiac regenerative therapy is conceivable by "foot-print free" reprogramming of somatic cells to induced pluripotent stem cells (iPSC). In this study, we report generation of foot-print free hiPSC through messenger RNA (mRNA) based reprograming. Subsequently, we characterize cardiomyocytes derived from these hiPSC using molecular and electrophysiological methods to characterize their applicability for regenerative medicine. Our results demonstrate that mRNA-iPSCs differentiate ontogenetically into cardiomyocytes with increased expression of early commitment markers of mesoderm, cardiac mesoderm, followed by cardiac specific transcriptional and sarcomeric structural and ion channel genes. Furthermore, these cardiomyocytes stained positively for sarcomeric and ion channel proteins. Based on multi-electrode array (MEA) recordings, these mRNA-hiPSC derived cardiomyocytes responded predictably to various pharmacologically active drugs that target adrenergic, sodium, calcium and potassium channels. The cardiomyocytes responded chronotropically to isoproterenol in a dose dependent manner, inotropic activity of nifidipine decreased spontaneous contractions. Moreover, Sotalol and E-4031 prolonged QT intervals, while TTX reduced sodium influx. Our results for the first time show a systemic evaluation based on molecular, structural and functional properties of cardiomyocytes differentiated from mRNA-iPSC. These results, coupled with feasibility of generating patient-specific iPSCs hold great promise for the development of large-scale generation of clinical grade cardiomyocytes for cardiac regenerative medicine. © 2014 Mehta et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161396
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0103485
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