The pulmonary microvasculature entraps induced vascular progenitor cells (iVPCs) systemically delivered after cardiac ischemia‐reperfusion injury: Indication for preservation of heart function via paracrine effects beyond engraftment.

Objective: Stem cell‐based regenerative therapies have been intensively studied with the aim to define an ideal cell type for the treatment of myocardial infarction. We tested systemically delivered, platelet‐targeted induced vascular progenitor cells (iVPCs) to study their potential to salvage damaged myocardium after ischemia‐reperfusion injury. Methods: Using a mouse model of ischemia‐reperfusion injury, we tested the potential of platelet‐targeted iVPCs (1 × 106 targ‐iVPCs) compared to non‐targ‐iVPCs and a saline control. Bioluminescence imaging, echocardiography, and histological analyses were performed. Results: Four weeks after ischemia‐reperfusion injury, systemic delivery of targ‐iVPCs led to reduced fibrosis and infarct size (PBS: 25.7 ± 3.9 vs targ‐iVPC: 18.4 ± 6.6 vs non‐targ‐iVPC: 25.1 ± 3.7%I/LV, P < 0.05), increased neovascularization, and restored cardiac function (PBS: 44.0 ± 4.2 vs targ‐iVPC: 54.3 ± 4.5 vs non‐targ‐iVPC: 46.4 ± 3.8%EF, P < 0.01). Cell tracking experiments revealed entrapment of intravenously injected iVPCs in the pulmonary microvasculature in both cell‐treated groups. Conclusions: Systemic delivery of iVPCs after cardiac ischemia‐reperfusion injury is limited by pulmonary entrapment of the cells. Nevertheless, targ‐iVPCs reduced infarct size, fibrosis, increased neovascularization, and most importantly retained cardiac function. These findings contribute to the mechanistic discussion of cell‐based therapy and ultimately identify activated platelet‐targeted iVPCs as candidates for cell therapy and also describe cell therapy benefits without the necessity of engrafting. [ABSTRACT FROM AUTHOR]