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

被引：13

作者：

Ziegler, Melanie ^{[1
]}

Haigh, Katharina ^{[2
]}

Thao Nguyen ^{[2
]}

Wang, Xiaowei ^{[1
,3
]}

Lim, Bock ^{[1
]}

Yap, May Lin ^{[1
]}

Eddy, Eleanor M. ^{[1
]}

Haigh, Jody J. ^{[2
]}

Peter, Karlheinz ^{[1
,3
]}

机构：

[1] Baker Heart & Diabet Inst, Atherothrombosis & Vasc Biol, POB 6492, Melbourne, Vic 3004, Australia

[2] Monash Univ, Mammalian Funct Genet Lab, Div Blood Canc, Australian Ctr Blood Dis, Melbourne, Vic, Australia

[3] Monash Univ, Dept Med, Melbourne, Vic, Australia

来源：

MICROCIRCULATION | 2019年 / 26卷 / 02期

基金：

英国医学研究理事会;

关键词：

cell delivery; cell tracking; ischemia-reperfusion injury; iVPC; myocardial infarction; regenerative cell therapy; PLURIPOTENT STEM-CELLS; MECHANISMS; THERAPY; REPAIR; MOUSE;

D O I：

10.1111/micc.12493

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 10(6) 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.

引用

页数：10