Biologic Induced Endogenous Cardiac Repair in Chronic Ischemic Heart Failure through Immunomodulation and Stromal Cell Reorganization

Chronic ischemic heart failure remains a global epidemic for which curative therapies are lacking. We report a first-in-class biologic that induces myocardial repair through multiple coordinated pathways including immune cell activation to promote anti-inflammation and stromal cell activation to promote extracellular matrix (ECM) remodeling. Proteomic profiling revealed a distinctive signature enriched in ECM reorganization and immune-modulatory pathways. In vivo, the biologic engages host tissue in a site-specific, biphasic repair program: (1) an initial immune activation phase, followed by (2) resolution characterized by the emergence of TREM2+ reparative macrophages and recruitment of stromal cells. These processes collectively re-establish a regenerative milieu reminiscent of the neonatal heart. Mechanistically, macrophages emerged as central drivers of repair, supported by dendritic cell mediated modulation of the immune niche. By integrating immune, stromal, and cardiomyocyte crosstalk, the biologic established a durable pro-reparative microenvironment that restored myocardial structure and function. This immune-guided strategy represents a new paradigm for treating chronic ischemic heart failure.<br><br><br><i>For inquiries regarding the contents of this dataset, please contact the Corresponding Author listed in the README.txt file. Administrative inquiries (e.g., removal requests, trouble downloading, etc.) can be directed to [e-mail]</i><br>