title: Non-invasive in vivo detection of peripheral limb ischemia improvement in the rat after adipose tissue-derived stromal cell transplantation.
abstract: BACKGROUND
  Adipose tissue-derived stromal cells (ADSCs) might help repair ischemic cardiovascular tissue. Their in vivo effects on the bioenergetics and microcirculation of ischemic muscle through a variety of non-invasive techniques was examined.
  
  
  RESULTS
  Unilateral hindlimb ischemia was induced in 42 rats. One day after femoral artery ligation, 6 rats per group were randomly injected with intramuscularly allogeneic ADSCs (10(6)-10(7)-10(8) cells/ml), conditioned media from ADSC cultures (conditioned media [CM], control), saline (control), allogeneic fibroblasts (10(7) cells/ml, control) or a non-conditioned medium (control). Rats underwent magnetic resonance angiography (MRA), short-time inversion recovery (STIR) edema-weighed imaging, proton MR spectroscopy ((1)H-MRS), thermal infrared imaging (IRI), immunoblotting and immunofluorescence analysis on both hindlimbs for 4 weeks. MRA and STIR documented arterial occlusion and ischemia, respectively. Muscle (1)H-MRS and IRI showed reductions of total creatine (tCr)/water and skin temperature in occluded hind limbs, respectively. At 4 weeks, the ADSC and CM groups had greater recovery of skin temperature and tCr/water in ischemic limbs compared with 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 and decrease fibrosis, largely through a paracrine mechanism. (1)H-MRS and IRI are useful tools to monitor attempts at salvaging the ischemic tissues with cell-derived novel therapies.
authors.affiliation: Cardiology Division and Center of Excellence on Aging, G. D'Annunzio University, Chieti, Italy.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Madonna
authors.forename: Stefano
authors.initials: S
authors.lastname: Delli Pizzi
authors.forename: Luigino
authors.initials: L
authors.lastname: Di Donato
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mariotti
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Carlo
authors.forename: Emilia
authors.initials: E
authors.lastname: D'Ugo
authors.forename: Maria Anna
authors.initials: MA
authors.lastname: Teberino
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Merla
authors.forename: Armando
authors.initials: A
authors.lastname: Tartaro
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
mesh_terms: D000185:Actinin / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D024061:Collagen Type III / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006614:Hindlimb; D007273:Injections, Intramuscular; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D018810:Magnetic Resonance Angiography; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012039:Regional Blood Flow; D012881:Skin Temperature; D017154:Stromal Cells / Q000378:metabolism / Q000637:transplantation*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D024061:Collagen Type III; D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000185:Actinin; D017228:Hepatocyte Growth Factor; D003401:Creatine