LB8. Allogeneic iPSC-Derived Cardiomyocyte Patch Therapy for Severe Ischemic Cardiomyopathy: Multicenter Clinical Study of Safety and Feasibility

Objective:
The primary purpose of this clinical trial was to investigate the safety and feasibility of human iPS cell-derived cardiomyocyte patches as a new therapy for patients with ischemic cardiomyopathy(ICM).

Methods:
This was a prospective, single-arm, open-label, multicenter study involving eight patients with ischemic cardiomyopathy. Patients were treated with full options of any medical and surgical treatments and eligible for enrollment if NYHA functional was class III or IV, and left ventricular ejection fraction (LVEF) was 35% or less. All patients received a single transplantation of human iPSC-derived cardiomyocyte patches and were subsequently placed on immunosuppressive therapy for three months to prevent rejection. The study's endpoints include LVEF, left ventricular remodeling, functional capacity and adverse events. In addition, safety evaluations, including tumorigenicity and arrhythmic events, were conducted, and a separate follow-up study was initiated to monitor long-term outcomes.

Results:
Among the eight patients evaluated, cardiac function did not show significant improvements, while exercise tolerance showed significant improvements at 52 weeks postoperatively compared with baseline. The mean LVEF(CT) increased from 28.7±6.8 % preoperatively to 33.0±6.0% at 52 weeks (p=.156). Left ventricular end-diastolic volume index (LVEDVI) decreased from 134.6±38.4 mL/m2 preoperatively 116.2±33.6 mL/m2 at 52 weeks (p=.44). NYHA functional class improved from III to II (four patients) or I (four patients) at 52 weeks. Peak VO₂ showed significant improvement, rising from 16.0±3.9 mL/kg/min preoperatively to 19.1±4.5 mL/kg/min at 52 weeks (p=.046). The 6-minute walk distance showed the trend of increase, rising from 427.0±83.9 m at baseline to 476.6±97.2 m at 52 weeks (p=.063). All eight patients survived through the latest follow-up (range, 2-5 years postoperatively). No tumors were detected, and no severe arrhythmia was observed up to 52 weeks.

Conclusions:
Although all patients show different improvement of cardiac functions in each, the study demonstrated significant improvements in exercise tolerance, with all patients surviving and no tumorigenesis, suggesting the potential clinical efficacy of iPS cell–derived cardiomyocyte patches. Although further investigations are needed, no safety concerns were observed, supporting the feasibility of this therapy of iPS cell–derived cardiomyocyte patches for no-option ICM patients.

Shigeru Miyagawa (1), Takuji Kawamura (1), Minoru Tabata (2), Akira Shiose (3), Hiroshi Niinami (4), Yoshiki Sawa (5), (1) Osaka University Graduate of Medicine, Suita, Osaka, (2) Juntendo University Hospital, Tokyo, Tokyo, (3) Kyushu University Hospital, Hakata, Fukuoka, (4) Tokyo Women's Medical University Hospital, Tokyo, Tokyo, (5) Osaka University Hospital, Suita, Osaka

Shigeru Miyagawa

Abstract Presenter

1994-1995 Surgeon in Osaka University Hospital  

1995-1997 General Surgeon in Ohtemae Hospital 

1997-1998 Cardiovascular Surgeon in Osaka Rousai Hospital  

1998-2004 Study in Post Graduate Course of Osaka University  

2004-2006 Cardiovascular Surgeon in Sakurabashi Watanabe Hospital 

2006-2009 Federal Republic of Germany Kerckhoff Klinik cardiovascular surgery visiting doctor, Research fellow in Max Plank institute 

2009-2009 Assistant professor in Osaka University 

2009-2014 Full‐time lecturer in Osaka University 

2014-2016 Specially Appointed Associate Professor in Osaka University (Dept. Immunology and Regenerative Medicine) 

2016- 2018 Specially Appointed Professor in Osaka University (Dept. Advanced Stem Cell Therapy) 

2018-2021 Specially Appointed Professor in Osaka University (Dept. Frontier Regenerative Medicine) 

2021-present Professor in Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine

Pavan Atluri

Commentator

Dr. Atluri is Director of Mechanical Circulatory Support and Heart Transplant and Director of Minimally Invasive and Robotic Cardiac Surgery at the University of Pennsylvania.