Transplantation of IPSC-Derived Cardiomyocyte Patches for Ischemic Cardiomyopathy

Abstract

Background: Despite 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). Methods: The patches were produced under clinical-grade conditions and displayed cardiogenic phenotypes and safety in 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. Results: Positron 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. Conclusions: This study is the first report of a successful transplant of hiPSC-CMs for severe ischemic cardiomyopathy.

Enhancing Mesenchymal Stem Cells (MSCs) for Therapeutic Purposes

“…We mention that one of the first clinical trials on engineered heart muscle in patients with terminal heart failure is ongoing, BioVAT-HF (ClinicalTrials.gov: NCT04396899). However, a recent report of in-human transplantation of an allogenic-induced pluripotent stem cell-derived cardiomyocytes patch into the epicardium of the anterior and lateral walls via the fourth intercostal space in a patient with ischemic cardiomyopathy has been currently published [137]. This report signals the safety and efficacy of these patches on NYHA class, left ventricular end systolic volume and Vo2 peak at the 1-year follow-up after transplantation [137].…”

“…However, a recent report of in-human transplantation of an allogenic-induced pluripotent stem cell-derived cardiomyocytes patch into the epicardium of the anterior and lateral walls via the fourth intercostal space in a patient with ischemic cardiomyopathy has been currently published [137]. This report signals the safety and efficacy of these patches on NYHA class, left ventricular end systolic volume and Vo2 peak at the 1-year follow-up after transplantation [137]. Moreover, the ESCORT trial on six patients referred to cardiac surgery has also demonstrated the technical feasibility of producing clinical-grade human embryonic stem cell-derived cardiovascular progenitors delivered in a fibrin epicardial patch, and supported their short-and mediumterm safety, thereby, setting the grounds for adequately powered efficacy studies [138].…”

Cardiac regeneration: Options for repairing the injured heart

“…The clinical symptoms apparently improved 6 months after surgery, without any major adverse events or changes in the cardiac wall 10.3389/fcvm.2022.981982 motion at the site of the transplant. However, more details need to be disclosed (114). Regardless, these first human clinical trials hold promises for the use of hPSC-CMs to repair cardiac damage (Figure 2).…”

MSCs vs. iPSCs: Potential in therapeutic applications

“…In addition, the next study involves the first human trial using clinical-grade hiPSC-CM patches to treat ischemic cardiomyopathy in a patient ( Miyagawa et al, 2022 ). Ischemic cardiomyopathy develops when a patient has a previous myocardial infarction.…”