Advances in Human iPSC Models and Stem Cell Secretome Therapy for Cardiometabolic Diseases

Abstract

Cardiometabolic diseases remain a major cause of global morbidity and mortality, with therapeutic progress limited by a persistent gap between preclinical models and clinical outcomes. This review highlights recent advances in human induced pluripotent stem cell (iPSC)-derived cardiac organoids and stem cell secretome–based regenerative strategies as emerging solutions to this challenge. Cardiac organoids recapitulate key features of human heart tissue and enable physiologically relevant modeling of ischemia–reperfusion injury, diabetes-related metabolic stress, and drug-induced cardiotoxicity. In parallel, regenerative cardiology has shifted toward cell-free approaches based on paracrine mechanisms, including secretome delivery via implantable immunoisolated devices. Remaining challenges include organoid standardization, secretome characterization, and evolving regulatory pathways. Continued integration of cardiac organoid platforms with secretome-based delivery technologies is expected to advance translational research and therapeutic development for cardiometabolic diseases.