期刊
BIOMATERIALS
卷 51, 期 -, 页码 138-150出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.01.067
关键词
Human pluripotent stem cells; Human fetal cardiomyocytes; Cardiomyocyte maturation; Cardiomyocyte contraction force
资金
- Netherlands Organization for Scientific Research (NWO-FOM) within the program on Mechanosensing and Mechanotransduction by Cells [FOM 09MMC02]
- Marie Curie COFUND programme U-Mobility
- Universidad de Malaga
- European Community [246550]
- Rembrandt Institute
- European Research Council [ERCAdG 323182]
- Netherlands Institute of Regenerative Medicine
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/C013202/1, NC/C013105/1, NC/K000225/1] Funding Source: researchfish
Cardiomyocytes from human pluripotent stem cells (hPSC-CM) have many potential applications in disease modelling and drug target discovery but their phenotypic similarity to early fetal stages of cardiac development limits their applicability. In this study we compared contraction stresses of hPSC-CM to 2nd trimester human fetal derived cardiomyocytes (hFetal-CM) by imaging displacement of fluorescent beads by single contracting hPSC-CM, aligned by microcontact-printing on polyacrylamide gels. hPSC-CM showed distinctly lower contraction stress than cardiomyocytes isolated from hFetal-CM. To improve maturation of hPSC-CM in vitro we made use of commercial media optimized for cardiomyocyte maturation, which promoted significantly higher contraction stress in hPSC-compared with hFetal-CM. Accordingly, other features of cardiomyocyte maturation were observed, most strikingly increased upstroke velocities and action potential amplitudes, lower resting membrane potentials, improved sarcomeric organization and alterations in cardiac-specific gene expression. Performing contraction force and electrophysiology measurements on individual cardiomyocytes revealed strong correlations between an increase in contraction force and a rise of the upstroke velocity and action potential amplitude and with a decrease in the resting membrane potential. We showed that under standard differentiation conditions hPSC-CM display lower contractile force than primary hFetal-CM and identified conditions under which a commercially available culture medium could induce molecular, morphological and functional maturation of hPSC-CM in vitro. These results are an important contribution for full implementation of hPSC-CM in cardiac disease modelling and drug discovery. (C) 2015 Elsevier Ltd. All rights reserved.
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