Abstract 16710: Induced Pluripotent Stem Cell-Derived Endothelial Cells From Diet-Induced Obesity Mice Exhibit Decreased Vascular Function in a Murine Model of Hindlimb Ischemia
Objective: Diabetes mellitus is a serious metabolic disease, which predisposes patients to an increased risk of micro- and macro-vascular complications. The aim of this study is to compare the function of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from normal and pre-diabetic mice in a murine model of hindlimb ischemia.
Approach and Results: iPSCs were generated from fibroblasts isolated from C57Bl/6 mice fed a normal or high-fat diet. These iPSCs were differentiated into iPSC-ECs using a directed monolayer approach. NOD/SCID mice underwent femoral artery ligation and were randomized into 3 groups receiving the following via intramuscular injection: 1) vehicle; 2) iPSC-ECs from control mice; and 3) iPSC-ECs from diet-induced obesity (DIO) mice (n=30 total). Hindlimb perfusion was measured with laser Doppler imaging (LDI), and evaluated histologically after day 14. In vitro functional analyses revealed that iPSC-ECs from DIO mice had significant decreased capacity to form capillary-like networks, diminished adhesion, migration, and proliferation. LDI showed significant reduction of perfusion in the hindlimbs of animals receiving iPSC-ECs from DIO mice. Histological analysis demonstrated a decrease in capillary density and the presence of atrophy and inflammatory cell infiltration. Microarray and RT-PCR analysis revealed an up-regulation in genes involved in cellular apoptosis and senescence pathways in iPSC-ECs from DIO mice.
Conclusions: This is the first study to compare the vascular function of iPSC-ECs from healthy and pre-diabetic mice in a hindlimb ischemia model. These results suggest that diabetic iPSC-ECs may not be suitable for vascular stem cell therapy.
- © 2013 by American Heart Association, Inc.