Safety confirmation of induced pluripotent stem cell-derived cardiomyocyte patch transplantation for ischemic cardiomyopathy: first three case reports

Frontiers in Cardiovascular Medicine

Cardiovascular Medicine

Yasushi Sakata¹  Shigeru Miyagawa²  Noriko Mochizuki-Oda²  Maki Takeda²  Tsubasa Mikami²  Emiko Ito²  Yukako Nitta²  Yoshito Ito²  Masao Sasai²  Daisuke Yoshioka²  Takuji Kawamura²  Takura Taguchi²  Ai Kawamura²  Masashi Kawamura²  Yusuke Misumi²  Tomomi Shimamoto²  Yoshiki Sawa³ 

[1] Department of Cardiology, Osaka University Graduate School of Medicine, Suita, Japan;Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan;Devision of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan;

关键词: cardiomyocyte patch transplantation;    iPS cells;    myocardial regenerative medicine;    heart failure;    immune response;    HLA antibodies;   

DOI  :  10.3389/fcvm.2023.1182209

 received in 2023-03-08, accepted in 2023-08-29,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionWith the expected increase in patients with heart failure and ischemic 15 cardiomyopathy, the development of myocardial regenerative medicine using cell transplantation as a novel treatment method is progressing. This first-in-human clinical trial aimed to confirm the safety of cardiomyocyte patch transplantation derived from allogeneic induced pluripotent stem (iPS) cells based on the results of several preclinical studies.Study designThe inclusion criteria were left ventricular ejection fraction of 35% or less; heart failure symptoms of New York Heart Association class III or higher despite existing therapies such as revascularization; and a 1-year observation period that included a 3-month immunosuppressive drug administration period after transplantation of iPS cell-derived cardiomyocyte patches to evaluate adverse events, cardiac function, myocardial blood flow, heart failure symptoms, and immune response.ResultsIn the first three cases of this trial, no transplanted cell-related adverse events were observed during the 1-year observation period, and improvement in heart failure symptoms was observed. In addition, improvements in left ventricular contractility and myocardial blood flow were observed in two of the three patients. Regarding immune response, an increase in transplant cell-specific antibody titer was observed in all three patients after immunosuppressive drug administration. In one patient with poor improvement in cardiac function and myocardial blood flow, an increase in antibody titer against HLA-DQ was observed even before cell transplantation.ConclusionsOur case findings demonstrate that the transplantation of iPS cell-derived cardiomyocyte patches for ischemic cardiomyopathy can be safely performed; however, further investigation of the therapeutic effect and its relationship with an immune response is needed by accumulating the number of patients through continued clinical trials.

【 授权许可】

Unknown   
© 2023 Kawamura, Ito, Ito, Takeda, Mikami, Taguchi, Mochizuki-Oda, Sasai, Shimamoto, Nitta, Yoshioka, Kawamura, Kawamura, Misumi, Sakata, Sawa and Miyagawa.