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Combinatorial polymer matrices enhance in vitro maturation of human induced pluripotent stem cell-derived cardiomyocytes

Authors
Chun, YW (Chun, Young Wook)Balikov, DA (Balikov, Daniel AFeaster, TK (Feaster, TromondaWilliams, CH (Williams, CharleSheng, CC (Sheng, Calvin C.)Lee, JB (Lee, Jung-Bok)Boire, TC (Boire, Timothy C.)Neely, MD (Neely, M. Diana)Bellan, LM (Bellan, Leon M.)Ess, KC (Ess, Kevin C.)Bowman, AB (Bowman, Aaron B.)Sung, HJ (Sung, Hak-Joon)Hong, CC (Hong, Charles C.)...
Issue Date
Oct-2015
Publisher
ELSEVIER SCI LTD
Citation
BIOMATERIALS, v.67, pp.52 - 64
Journal Title
BIOMATERIALS
Volume
67
Start Page
52
End Page
64
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/147114
DOI
10.1016/j.biomaterials.2015.07.004
ISSN
0142-9612
Abstract
Cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) hold great promise for modeling human heart diseases. However, iPSC-CMs studied to date resemble immature embryonic myocytes and therefore do not adequately recapitulate native adult cardiomyocyte phenotypes. Since extracellular matrix plays an essential role in heart development and maturation in vivo, we sought to develop a synthetic culture matrix that could enhance functional maturation of iPSC-CMs in vitro. In this study, we employed a library of combinatorial polymers comprising of three functional subunits - poly-epsilon-caprolacton (PCL), polyethylene glycol (PEG), and carboxylated PCL (cPCL) as synthetic substrates for culturing human iPSC-CMs. Of these, iPSC-CMs cultured on 4%PEG-96%PCL (each % indicates the corresponding molar ratio) exhibit the greatest contractility and mitochondrial function. These functional enhancements are associated with increased expression of cardiac myosin light chain-2v, cardiac troponin I and integrin alpha-7. Importantly, iPSC-CMs cultured on 4%PEG-96%PCL demonstrate troponin I (TnI) isoform switch from the fetal slow skeletal TnI (ssTnI) to the postnatal cardiac TnI (cTnI), the first report of such transition in vitro. Finally, culturing iPSC-CMs on 4%PEG-96%PCL also significantly increased expre
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