Cardiac Atrial Appendage Stem Cells Embedded in Elastin-like Recombinamer Hydrogel for Cardiac Repair After Acute MI: A Pilot Study

Myocardial infarction (MI) causes extensive cardiomyocyte loss and adverse remodeling, frequently progressing to heart failure. Although stem cell-based therapies are being investigated for cardiac repair, clinical outcomes remain modest. Cardiac atrial appendage stem cells (CASCs) harbor cardiomyogenic potential, making them promising candidates for cardiac regeneration. This proof-of-concept pilot study investigates the feasibility and preliminary therapeutic potential of delivering CASCs within an elastin-like recombinamer (ELR) hydrogel scaffold following MI. MI was induced in rats by permanent ligation of the left anterior descending coronary artery. Immediately after occlusion, CASCs (MI+C), ELR hydrogel (MI+H), or CASCs embedded in ELR hydrogel (MI+C+H) were injected intramyocardially into the peri-infarct region. MI and SHAM-operated animals served as controls. Four weeks post-MI, echocardiography showed a large, non-significant left ventricular ejection fraction improvement in MI+C+H versus MI, with a trend toward reduced end-diastolic volume. MI+C+H significantly improved anterior wall thickness versus MI+H, with favorable trends for MI+C. Wall motion score index showed a similar large, non-significant effect. Transcriptomics suggested the MI+C+H molecular profile reflected complementary contributions of both monotherapies rather than distinct synergistic mechanisms. These preliminary findings support ELR-mediated CASC delivery and suggest potential benefits for preserving cardiac function and limiting adverse remodeling, warranting confirmation in adequately powered studies.