CAR-CD34 (+) hematopoietic stem/progenitor cells produced in vivo protect against thoracic aortic aneurysm and dissection.

Abstract

Thoracic aortic aneurysm and dissection is one of the most devastating cardiovascular diseases, with limited medical intervention options. This study aims to develop chimeric antigen receptor-engineered CD34⁺ hematopoietic stem/progenitor cells and evaluate their effects on repairing endothelial cell injuries in a murine model. All animal experiments were performed in male mice. We design a chimeric antigen receptor containing a single-chain variable fragment targeting VCAM-1 and a VEGFA activation domain. A ligand-mediated lipid nanoparticle delivery system was used to engineer circulating CD34⁺ cells for transient and tunable chimeric antigen receptor expression. In vitro studies show that the engineered cells exhibit improved differentiation, proliferation, migration, adhesion, and tube formation. They successfully restore endothelial function, strengthened cell junctions, suppressed inflammatory response, and blocked disease progression. This study demonstrates that chimeric antigen receptor technique can effectively equip CD34⁺ hematopoietic stem/progenitor cells to target injured vascular intima, offering a promising approach for treating cardiovascular diseases.