Objectives: Myocardial restoration through transplantation of human embryonic stem cells (hESC) may broaden the spectrum of surgical treatment of heart disease in the future. A major limitation is, early, donor-cell death. Here, we seek to enhance myocardial repair following transplantation of cardiomyocyte-enriched hESC by cyto-protective (Allopurinol+Uricase) and anti-inflammatory (Ibuprofen) agents.
Methods: We injected 500,000 (15% hESC-derived cardiomyocytes) Green-Fluorescent-Protein-positive (GFP+) hESC in the infarcted area following LAD-ligation in SCID-beige mice. In Group I, 1.6 mg Allopurinol and 0.2 mg of Uricase were injected i.p. for 3 days prior to cell transplantation. In Group II, 0.35mg/ml of Ibuprofen were supplemented to the drinking water for 7 days prior until 7 days post cell transplantation. In Group III only hESC without additional treatment were transplanted. Group IV involved infarcted controls and Group V involved sham operated mice (all groups: n=5). We evaluated heart function (Ejection Fraction: EF) by MRI (4.7 Tesla) three weeks later. The hearts were harvested for histology.
Results: hESC formed clusters within the infarcted area and stained for GFP and Human anti-nuclear antigen. They expressed cardiac markers such as a-sarcomeric actin and Connexin 43. Despite extensive cell loss, hESC resulted in improvement of heart function, which was best in the Ibuprofen- and Allopurinol-treated groups, compared to the infarcted controls [EF: Group I: 76.6±8.6% (p<0.01), Group II: 78.6±7.3% (p<0.01), Group III: 57.7±7.5, Group IV: 43.5±4.3, Group V: 66.3±7.8%]. We did not observe tumors.
Conclusions: Cyto-protective and anti-inflammatory agents can significantly enhance hESC-engraftment and myocardial restoration following transplantation into the injured heart.

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