The Impact of Primary Myoblast Transplantation on Functional Vasodilation Following Arteriogenesis in Mice with Diet‐Induced Obesity

Abstract

Peripheral arterial occlusive disease (PAOD) is characterized by reduced blood flow to the lower limbs, causing claudication and tissue loss. Proximal collateral arteries are natural bypasses to atherosclerotic occlusions in major arteries. A variety of cell‐based therapies have been tested clinically to enhance collateral arteriogenesis. Unfortunately, their efficacy has been poor, despite promising results from early clinical and preclinical studies, possibly because most preclinical studies are performed with mice that lack co‐morbidities present in most patients that are known to impair arteriogenesis. Therefore, additional cell‐types must be explored in animal models that more closely recapitulate the clinical phenotype to determine if pro‐regenerative therapies are a viable treatment for PAOD. Myogenic cells are an attractive candidate, given their co‐localization with the skeletal muscle vasculature niche and their ability to enhance angiogenesis. Therefore, we tested the hypothesis that primary myoblasts would rescue functional vasodilation in the superficial gracilis collateral following arteriogenesis in mice with diet‐induced obesity (DIO).In these studies, C57Bl/6 mice were fed a high‐fat diet from 6‐weeks of age; experiments were performed at about 4‐months of age. First, we performed a pilot study to evaluate functional vasodilation (vasodilation in response to electrically‐stimulated gracilis muscle contraction) in unoperated animals. As expected, vasodilation was impaired in the right (42±4 vs. 58±4 μm) and left (40±5 vs. 52±5 μm), as compared to lean controls.Having established impaired vasodilation in mice with DIO, we ligated the femoral artery in mice to model obesity and the chronic ischemia aspect of PAOD and measured functional vasodilation at day‐7 following surgery. Pilot data suggests that functional vasodilation is reduced in mice with DIO at day‐7 following surgery (resting: 80±10 μm, dilated: 82±8 μm) and that cell transplantation appears to enhance arteriogenesis and improve functional vasodilation (resting: 93±8 μm, dilated: 108±8 μm). Additional experiments are necessary to confirm these findings, but the data suggest that myoblasts strengthen the arteriogenic response. Future studies may involve additional time points to investigate the time course and duration of myoblast‐rescued arteriogenesis and functional vasodilation following arterial occlusion.Support or Funding InformationResearch was funded by the California Institute of Regenerative Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.