Type 2 diabetes impairs the ability of skeletal muscle pericytes to augment postischemic neovascularization in db/db mice

Peripheral artery disease is an atherosclerotic occlusive disease that causes limb ischemia and has few effective non-interventional treatments. Stem cell therapy is promising, but concomitant diabetes may limit its effectiveness. We evaluated the therapeutic potential of skeletal muscle pericytes to augment postischemic neovascularization in wild type and type 2 diabetic (T2DM) mice. Wild type C57BL/6J and leptin receptor spontaneous mutation db/db T2DM mice underwent unilateral femoral artery excision to induce limb ischemia. Twenty-four hours after ischemia induction, CD45-CD34-CD146+ skeletal muscle pericytes or vehicle control were transplanted into ischemic hindlimb muscles. At postoperative day 28, pericyte transplantation augmented blood flow recovery in wild type mice (79.3{plus minus}5% vs. 61.9{plus minus}5%; p=0.04), but not in T2DM mice (48.6%{plus minus}6% vs. 46.3{plus minus}5%; p=0.51). Pericyte transplantation augmented collateral artery enlargement in wild type (26.7{plus minus}2 μm vs. ...