Adipose tissue-derived stromal cells (ADSCs) may help repair ischemic cardiovascular tissue. We examined their in vivo effects on the bioenergetics and microcirculation of ischemic muscle.Methods and Results
Unilateral hind limb ischemia was induced in 42 rats. One day after femoral artery ligation, 6 rats per group were randomly injected intramuscularly allogeneic ADSCs (10^6-10^7-10^8 cells/mL); or conditioned media from ADSC cultures (CM, control); or phosphate-buffered saline (control); or allogeneic fibroblasts (10^7 cells/mL, control); or non-conditioned medium (control). Rats underwent magnetic resonance angiography (MRA); short time inversion recovery (STIR) edema-weighed imaging; proton MR spectroscopy (1H-MRS); thermal infrared imaging (IRI), immunoblotting and immunofluorescence analysis on both hind limbs for 4 weeks.Methods and Results
MRA and STIR images documented arterial occlusion and ischemia, respectively. Muscle 1H-MRS and IRI showed reductions of tCr/water and skin temperature in occluded hind limbs, respectively. At 4 weeks, ADSC and CM groups had greater recovery of skin temperature and tCr/water in ischemic limbs compared with all controls (P < 0.01), with increased expression of α-sarcomeric actinin and vascular growth factors, such as hepatocyte growth factor (HGF), increased vessel density (capillaries, arterioles and venules) and less type III collagen.Conclusions
Allogeneic ADSCs improve ischemic muscle metabolism, increase neovasculogenesis within microcirculation and decrease fibrosis, largely through a paracrine mechanism, with a potential role of HGF. 1H-MR spectroscopy and IR thermography are useful tools to monitor attempts at salvaging the ischemic tissues with cell or cell-derived novel therapies.