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The pulmonary microvasculature entraps induced vascular progenitor cells ( iVPC s) systemically delivered after cardiac ischemia‐reperfusion injury: Indication for preservation of heart function via paracrine effects beyond engraftment
Author(s) -
Ziegler Melanie,
Haigh Katharina,
Nguyen Thao,
Wang Xiaowei,
Lim Bock,
Yap May Lin,
Eddy Eleanor M.,
Haigh Jody J.,
Peter Karlheinz
Publication year - 2019
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12493
Subject(s) - medicine , ischemia , cardiac function curve , progenitor cell , reperfusion injury , neovascularization , cardiology , angiogenesis , stem cell , heart failure , biology , genetics
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 ( iVPC s) 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 iVPC s (1 × 10 6 targ‐ iVPC s) compared to non‐targ‐ iVPC s and a saline control. Bioluminescence imaging, echocardiography, and histological analyses were performed. Results Four weeks after ischemia‐reperfusion injury, systemic delivery of targ‐ iVPC s 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 iVPC s in the pulmonary microvasculature in both cell‐treated groups. Conclusions Systemic delivery of iVPC s after cardiac ischemia‐reperfusion injury is limited by pulmonary entrapment of the cells. Nevertheless, targ‐ iVPC s 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 iVPC s as candidates for cell therapy and also describe cell therapy benefits without the necessity of engrafting.