2018
DOI: 10.18632/aging.101411 View full text |Buy / Rent full text
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Abstract: The use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Although many approaches have been reported to improve the maturation of hiPSC-CMs, the elucidation of the process of maturation is crucial. We applied a small-molecule-based differentiation method to generate cardiomyocytes (CMs) with multiple aggregation forms. The motion analysis revealed significant physical differences in the different… Show more

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“…Immaturity of somatic cells differentiated from pluripotent stem cells has been reported 51 , 52 . For iPSC-derived cardiomyocytes, mechanical and or electrophysiological stimulation enhances their structural maturity in vitro 53 so it is conceivable that cochlear hair cells developing within otic organoids may require acoustic stimulation to become fully functional. This is consistent with the functional maturation of cochlear hair cells and the development of hearing in neonatal mice 54 , however to improve the utility of our inner ear organoid culture to the point where we can investigate the possible contribution of acoustic stimulation, we need to manipulate additional signalling molecules that could amplify the otic induction process.…”
Section: Discussionmentioning
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“…Immaturity of somatic cells differentiated from pluripotent stem cells has been reported 51 , 52 . For iPSC-derived cardiomyocytes, mechanical and or electrophysiological stimulation enhances their structural maturity in vitro 53 so it is conceivable that cochlear hair cells developing within otic organoids may require acoustic stimulation to become fully functional. This is consistent with the functional maturation of cochlear hair cells and the development of hearing in neonatal mice 54 , however to improve the utility of our inner ear organoid culture to the point where we can investigate the possible contribution of acoustic stimulation, we need to manipulate additional signalling molecules that could amplify the otic induction process.…”
Section: Discussionmentioning
“…In our previous study, 30 we observed a net‐shaped CM cluster which beat in a certain direction with robust contraction shown developed myofibril structure. To detect the relationship of cell alignment and hPSC‐CMs maturation, we seed hPSC‐CMs on the micron‐scale patterned groove and found that either single CM or cardiomyocytes clusters are oriented along the grooves.…”
Section: Introductionmentioning
“…Each cardiomyocyte was analyzed using ImageJ software with standard analysis plugins for average sarcomere length and cell area. More than 60 cells were analyzed for each group 6 , 13 . The antibodies used in this study are listed in Table S3 .…”
Section: Methodsmentioning
“…However, hPSC-CMs generated by current protocols are more similar to cardiomyocytes at embryonic or early fetal stages 9 . Previous reports have shown that electrical stimulation, small molecules, and tissue engineering can promote cardiomyocyte maturation 7 , 11 - 13 . However, it is still difficult to obtain fully matured cardiomyocytes from hPSCs, and the mechanism for cardiomyocyte maturation is still largely unknown.…”
Section: Introductionmentioning