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Category CDBセミナー
Date and Time 2017-04-18 15:30 - 16:30
Venue Seminar Room A7F
Speaker Hidetoshi Masumoto
Affiliation Department of Cardiovascular Surgery, Kyoto University Hospital
Title Three-dimensional heart tissues generated from human iPS cells for regenerative therapy and disease modeling
Poster click here to download(PDF)
Host Shigeo Hayashi
Summary Three-dimensional bioengineered constructs recapitulating heart tissue would be promising for cardiac repair and disease modeling. Utilizing cardiovascular populations (cardiomyocytes [CMs]/ endothelial cells [ECs]/ vascular mural cells [MCs]) from mouse ES cells (mESCs), we generated mESC-derived cardiac tissue sheets (CTSs). The transplantation of the CTSs onto a rat myocardial infarction (MI) model exhibited a functional recovery mainly mediated by neovascularization which was diminished in a transplantation of sheets lacking CMs (EC/MC sheets), indicating that CMs play a central role (Stem Cells, 2012). To extend the strategy toward human iPS cells (hiPSCs), we simultaneously induced multiple cardiovascular populations by sequential supplementation of cytokines, and generated self-pulsating hiPSC-CTSs which exhibited myocardial regeneration in vivo (Sci Rep, 2014). To further promote tissue regeneration, we engineered thicker CTSs from mESCs using gelatin hydrogel microspheres leading to facilitated myocardial regeneration supported by functional capillary network in vivo (Sci Rep, 2015). We further generated thicker hiPSC-CTSs (hiPSC-derived cardiac tissue; HiCT) and confirmed an excellent functional recovery in rat and porcine MI models, and in a δ-sarcoglycan-deficient dilated cardiomyopathy hamster model. We recently developed cylindrical engineered cardiac tissues (ECTs) using hiPSC-derived cardiovascular cells and biomaterials. Incorporation of multiple cardiovascular populations enhanced electromechanical function and facilitated ECT maturation (Sci Rep, 2016). The ECTs were advantageous for functional recovery in vivo, and can be prepared as a larger mesh-like format suitable for large animal pre-clinical and clinical studies (Sci Rep, in press). These hiPSC-derived heart tissues may also contribute to disease modeling such as an in vitro drug-induced Torsade de Pointes (polymorphic lethal arrhythmia) model (Nat Commun, in revision) or disease-specific iPSC-derived ECTs which can be used for drug development and safety tests. Here we demonstrated that hiPSC-derived three-dimensional heart tissues hold novel properties relevant for clinical translation.
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