Kuroda Yuki, Iida Jun, Murata Kozue, Hori Yuki, Kobiki Jumpei, Minatoya Kenji, Masumoto Hidetoshi
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Clinical Translational Research Program, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
JTCVS Open. 2025 Mar 17;25:154-162. doi: 10.1016/j.xjon.2025.03.006. eCollection 2025 Jun.
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).
We prepared cell sheet-shaped VCM with hiPSC-derived cardiomyocytes and vascular cells using 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 1 week after MI induction.
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, = .048). The mean conduction velocity between the remote and MI sites was numerically higher in the VCM group compared with the Sham group (2.84 m/s vs 1.74 m/s). One of the 3 animals in the VCM group demonstrated 2 independent origins of excitation corresponding to the pacing sites when simultaneous pacing of the remote and MI sites was performed 1 week after MI induction. Histologic 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.
The transplantation of VCM demonstrated a potential for improving conduction disturbances in MI.
证明人诱导多能干细胞（hiPSC）来源的血管化心脏微组织（VCM）移植可改善心肌损伤（MI）后的传导障碍。
我们使用动态摇摆培养法，用hiPSC来源的心肌细胞和血管细胞制备了细胞片状VCM。我们通过心外膜冷冻消融在免疫抑制的小型猪（VCM组和假手术组；n = 3）中诱导MI，并在MI诱导后立即移植VCM。在MI诱导前和诱导后1周，对猪进行心外膜电解剖标测。
MI诱导后1周，在窦性心律期间，两组MI部位的平均电位均降低（VCM组从11.05 mV降至1.74 mV，假手术组从8.72 mV降至2.70 mV，P = 0.048）。与假手术组相比，VCM组远程部位和MI部位之间的平均传导速度在数值上更高（2.84 m/s对1.74 m/s）。VCM组3只动物中的1只在MI诱导后1周对远程部位和MI部位进行同步起搏时，表现出与起搏部位相对应的2个独立兴奋起源。组织学检查证实VCM已植入MI区域表面。此外，我们证实与假手术组相比，VCM移植组在损伤后1周MI区域的心肌组织保持更完整，这表明这有助于减少传导障碍。
VCM移植显示出改善MI传导障碍的潜力。
