Abstract
Various cell-based therapies are currently investigated in an attempt to tackle the high morbidity and mortality associated with heart failure. The need for these therapies to move towards the clinic is pressing. Therefore, preclinical large animal studies that use non-autologous cells are needed to evaluate their potential. However, non-autologous cells are highly immunogenic and trigger immune rejection responses resulting in potential loss of efficacy. To overcome this issue, adequate immunosuppressive regimens are of imminent importance but clear guidelines are currently lacking. In this review, we assess the immunological barriers regarding non-autologous cell transplantation and immune modulation with immunosuppressive drugs. In addition, we provide recommendations with respect to immunosuppressive regimens in preclinical cardiac cell-replacement studies.
Highlights
mycophenolate mofetil (MMF) in combination with calcineurin inhibitor therapy has been shown to be superior to azathioprine in preventing acute rejection episodes, development of coronary allograft vasculopathy, and mortality despite slightly higher infection rates [47, 48]
For preclinical studies, we should aim for high standards when performing immunosuppression
Pigs 60-min LAD occlusion Not clearly defined 2 × 10^6 hiPSC-CMs alone hiPSC-CMs, -ECs,SMC combined Cells combined in patch Xenogeneic Intramyocardial injection or fibrin patches with IGF-1 15 min after IR
Summary
Clinical Relevance Adequate immunosuppressive protocols are of great importance to enhance the predictive value of cardiac cell-replacement studies for clinical translation. This manuscript provides important insights and recommendations for proper immunosuppressive regimen design in preclinical large animal models. Ischemic heart disease, including myocardial infarction (MI), results in permanent and progressive loss of myocardial contractility. With more than 37.7 million patients, heart failure (HF), including HFrEF, is a substantial clinical problem and currently the fastest growing cardiovascular condition globally [2]. Current treatment options for HF are mostly aiming at reducing symptoms or delaying disease progression at best [4]
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