iPS心組織で電気信号の流れを改善~ブタ心筋傷害モデルを用いた検討~

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2025-03-28 京都大学

京都大学医学部附属病院の升本英利特定准教授(兼:理化学研究所上級研究員)と黒田悠規博士課程学生らの研究グループは、ヒトiPS細胞から作製した血管化心臓組織を、心筋障害を持つミニブタの心臓に移植し、電気信号の伝導障害が改善されることを確認しました。この成果は、iPS細胞を用いた心臓再生医療の新たな可能性を示すもので、今後の治療法開発に寄与することが期待されます。詳細は2025年3月17日付の国際学術誌「JTCVS Open」にオンライン掲載されました。

<関連情報>

ブタ⼼筋障害モデルにおけるヒト iPS細胞由来⾎管化⼼臓マイクロ組織移植による電気伝導障害の改善 Transplantation of vascularized cardiac microtissue from human iPS cells improves impaired electrical conduction in a porcine myocardial injury model

Yuki Kuroda MD, Jun Iida MD, Kozue Murata PhD, Yuki Hori MD, Jumpei Kobiki MD, Kenji Minatoya MD,PhD, Hidetoshi Masumoto MD,PhD
JTCVS Open  Available online: 17 March 2025
DOI:https://doi.org/10.1016/j.xjon.2025.03.006

Graphical abstract

Abstract

Objective
To demonstrate that the transplantation of human induced pluripotent stem cell (hiPSC)-derived vascularized cardiac microtissue (VCM) can improve conduction disturbances after myocardial injury (MI).

Methods
We prepared cell sheet-shaped VCM with hiPSC-derived cardiomyocytes and vascular cells utilizing dynamic rocking culture. We induced MI via epicardial cryoablation in immunosuppressed crown minipigs (VCM and sham groups; N=3) and transplanted the VCMs immediately after MI induction. The pigs underwent epicardial electroanatomical mapping immediately before and one week after MI induction.

Results
One week after MI induction, mean electrical potentials at the MI site decreased in both groups during sinus rhythm (from 11.05 to 1.74 mV in the VCM group, and from 8.72 to 2.70 mV in the sham group, P=0.048). The mean conduction velocity between the remote and MI sites was numerically higher in the VCM group compared to the Sham group (2.84 m/s versus 1.74 m/s). One of the three animals in the VCM group demonstrated two independent origins of excitation corresponding to the pacing sites when simultaneous pacing of the remote and MI sites was performed one week after MI induction. Histological examination confirmed that the VCM had engrafted on the surface of the MI region. Furthermore, we confirmed that the myocardial tissue in the MI region remained more intact one week after injury in the VCM transplantation group compared to the sham group, suggesting that this contributed to the reduction of conduction disturbances.

Conclusions
The transplantation of VCM demonstrated a potential for improving conduction disturbances in MI.

医療・健康
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