MRI Studies of Cryoinjury Infarction in Pig Hearts: Ii. Effects of Intrapericardial Delivery of Adipose-derived Stem Cells (ADSC) Embedded in Agarose Gel

The purpose was to assess effects of intrapericardially deposited adipose-derived stem cells (ADSC) as a source of angiogenic factors on cryoinjury infarction. To enhance this effect and reduce incorporation of ADSC into tissue, the cells were immobilized in agarose gel patches transplanted onto cryoinjured epicardium. In domestic pigs (15-20 kg) the left ventricular (LV) anterior wall of exposed hearts was cryoinjured using aluminum rod (Φ=25 mm) cooled in liquid nitrogen. Sterilized circular patches made of agarose gel were placed in a nylon bag and sutured to cryoinjured epicardium. In 4 pigs, the patches contained 650,000 human ADSCs; in control animals patches were cell-free (n=2) or no patches were implanted (n=2). Cine and T(1)-weighted MRI was performed in vivo weekly (4 weeks) after injury using a 3 T imager. Following baseline imaging, a 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 were assessed using MnCl(2) (70 micromol/kg/14 min). In all pigs, 5 × 10(6) 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 necrotic areas. Four-week infarction areas were hypokinetic and 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), which correlated with 3 times higher microvascular density in treated hearts. LV wall thickening was partially restored by ADSC treatment. ADSC-containing patches attached to cryoinjured epicardium greatly improved perfusion and microvascular density of scar tissue.