Functional and Electrical Integration of Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Myocardial Infarction Rat Heart.

作者: Takahiro Higuchi , Shigeru Miyagawa , James T. Pearson , Satsuki Fukushima , Atsuhiro Saito

DOI: 10.3727/096368914X685799

关键词: CardiologyActin cytoskeletonMyosinPathologyTransplantationMyocyteMyocardial infarctionBiologyEjection fractionInduced pluripotent stem cellCardiac muscleInternal medicine

摘要: In vitro expanded beating cardiac myocytes derived from induced pluripotent stem cells (iPSC-CMs) are a promising source of therapy for regeneration. Meanwhile, the cell sheet method has been shown to potentially maximize survival, functionality, and integration transplanted into heart. It is thus hypothesized that iPSC-CMs in manner may contribute functional recovery via direct mechanical effects on myocardial infarction (MI) F344/NJcl-rnu/rnu rats were left coronary artery ligated (n = 30), followed by transplantation Dsred-labeled iPSC-CM sheets murine origin over infarct heart surface. Effects treatment assessed, including vivo molecular/cellular evaluations using synchrotron radiation scattering technique. Ejection fraction activation interval significantly greater day 3 onward after compared those sham operation. A number present surface expressing myosin or connexin 43 2 weeks, assessed immunoconfocal microscopy, while mitochondria gradually showed mature structure as electron microscopy. Of note, X-ray diffraction identified 1,0 1,1 equatorial reflections attributable actin-myosin lattice planes typical organized muscle fibers within at 4 suggesting cyclic systolic mass transfer actin filaments iPSC-CMs. Transplantation yielded electrical with contraction rat MI heart, indicating this strategy be replacement therapy.

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