1094-Cardiac Fibrosis Clearance and Myocardial Regeneration

This research introduces pleiotropic chimeric antigen receptor-monocytes (pCAR-Mos) as a dual-action cell therapy designed to treat heart failure following a myocardial infarction. By engineering monocytes to target fibroblast activation protein (FAP) and secrete the regenerative protein Agrin, the study demonstrates a synergistic approach that clears pathogenic fibrosis while simultaneously promoting cardiomyocyte proliferation and angiogenesis. Unlike traditional CAR-T or CAR-macrophage treatments, these engineered monocytes show superior cardiac homing capabilities and a more favorable distribution within injured tissues. Experimental results in mice reveal that this treatment significantly reduces infarct size, restores cardiac function, and reshapes the fibrotic microenvironment without systemic toxicity. Single-nuclear RNA sequencing further confirms that pCAR-Mos effectively eliminate pathological fibroblast subsets and foster a pro-regenerative environment for heart repair. In summary, the study presents a reversible and highly efficient adoptive cell therapy that addresses the critical medical need for both scar reduction and muscle regrowth in ischemic heart disease.

References:

• Wu Z, Zou X, Chen C, et al. Engineered CAR-monocytes coordinate fibrosis clearance and cardiac regeneration following myocardial infarction[J]. Cell Stem Cell, 2026.