Abstract 12390: Epicardial Implantation of Agarose Gel Patches Containing Adipose-Derived Stem Cells Improved Perfusion of Cryoinjury Infarction in Pig Hearts
Purpose: To assess effects of intrapericardial adipose-derived stem cells (ADSC) as a source of growth factors on cryoinjury infarction perfusion and vascularization. To maximize this effect and minimize incorporation of ADSC into the tissue we encapsulated them into agarose gel patches transplanted onto cryoinjured epicardium.
Methods: In domestic pigs (15–20 kg) the left ventricular (LV) anterior wall of exposed hearts was cryoinjured by 25-mm aluminum rod cooled in liquid nitrogen. Sterilized circular patches made of agarose gel (d=19 mm, ∼2 mm thick) were placed in nylon bag and sutured to cryoinjured epicardium. In 4 pigs patches contained 650,000 of human ADSCs; in control animals patches were cell-free (n=2) or no patches were implanted (n=2). After injury T1-weighted MRI was performed in vivo weekly (4 weeks) in a 3T imager. Following baseline imaging double bolus of gadopentate dimeglumine was injected (GdDTPA, 0.05 and 0.15 mmol/kg) and serial short axis images were acquired. In the 4-week ADSC-treated group, 2 pigs were assessed using GdDTPA and 2 pigs using MnCl2 (70 micromol/kg/14 min). In all pigs 5x106 NIR fluorescent microspheres (15 μm FMS, 645/680 nm) were injected into the hearts, which were excised, sliced and examined with fluorescence imaging for FMS content. Triphenyltetrazolium chloride (TTC) staining was used to determine infarct areas.
Results: The infarct areas appeared hyperintensive on Gd-enhanced MR images, hypointensive on Mn-enhanced images and were TTC-negative. First-pass Gd enhancement kinetics was faster in the infarct area of ADSC-treated hearts: 152±89 vs. 54±5.3% of normal in control (p=0.03). Accordingly, FMS fluorescence was much higher in the treated infarcts (144±59% of remote, n=4) relative to control hearts (58±13%, n=4, p=0.01), which correlated with 3 times higher microvascular density in treated hearts.
Conclusions: ADSC-containing patches attached to the cryoinjured epicardium greatly improved perfusion and microvascular density of scar tissue.
- © 2010 by American Heart Association, Inc.