Transplantation of IPSC-Derived Cardiomyocyte Patches for Ischemic Cardiomyopathy

Author:

Miyagawa ShigeruORCID,Kainuma Satoshi,Kawamura Takuji,Suzuki Kota,Ito Yoshito,Iseoka Hiroko,Ito Emiko,Takeda Maki,Sasai Masao,Mochizuki-Oda Noriko,Shimamoto Tomomi,Nitta Yukako,Dohi Hiromi,Watabe Tadashi,Sakata Yasushi,Toda Koichi,Sawa YoshikiORCID

Abstract

AbstractBackgroundDespite major therapeutic advances, heart failure remains a life-threatening disorder, with 26 million patients worldwide, causing more deaths than cancer as a non-communicable disease. Therefore, novel strategies for the treatment of heart failure continue to be an important clinical need. Based on preclinical studies, allogenic human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches have been proposed as a potential therapeutic candidate for heart failure. We report the implantation of allogeneic hiPSC-CM patches in a patient with ischemic cardiomyopathy (ClinicalTrials.gov, #jRCT2053190081).MethodsThe patches were produced under clinical-grade conditions and displayed cardiogenic phenotypes and safetyin vivo(severe immunodeficient mice) without any genetic mutations in cancer-related genes. The patches were then implanted via thoracotomy into the left ventricle epicardium of the patient under immunosuppressive agents.ResultsPositron emission tomography and computed tomography confirmed the possible efficacy and did not detect tumorigenesis in either the heart or other organs; the clinical symptoms improved 6 months after surgery, without any major adverse events, suggesting that the patches were well-tolerated. Furthermore, changes in the wall motion in the transplanted site were recovered, suggesting a favorable prognosis and the potential tolerance to exercise.ConclusionsThis study is the first report of a successful transplant of hiPSC-CMs for severe ischemic cardiomyopathy.

Publisher

Cold Spring Harbor Laboratory

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1. ONO-1301 enhances post-transplantation survival of human induced pluripotent stem cell-derived cardiac tissue sheet by promoting angiogenesis;The Journal of Heart and Lung Transplantation;2023-06

2. Advances in 3D Organoid Models for Stem Cell-Based Cardiac Regeneration;International Journal of Molecular Sciences;2023-03-08

3. Cardiac regeneration: Options for repairing the injured heart;Frontiers in Cardiovascular Medicine;2023-01-12

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