NEW TREATMENT FOR MYOCARDIAL INFARCTION BY XENO-FETAL CARDIOMYOCYTE TRANSPLANTATION

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Background. Experimental allografting of fetal cardiomyocytes has been performed successfully. In this study, we attempted to transplant rat fetal cardiomyocytes into the hearts of mice by blocking the CD28/B7 co-stimulatory pathway via CTLA4-Ig gene transfer.Methods. Fetal cardiomyocytes derived from Dark Agouti (DA) rat were infected with CTLA4-Ig-expressing adenovirus vectors (AdCTLA) and injected directly into the normal myocardium of C3H/He mice (n=15). For control, cells infected with β-Gal-expressing adenovirus vector (AdRL) and cells without infection were injected into additional mice (n=30). The percentages of cardiomyocytes infection by AdRL or AdCTLA were estimated by X-gal staining or immunostaining with anti-CTLA4-Ig antibody. Mice were killed at 2 (n=5), 4 (n=5), and 8 (n=5) weeks after xenotransplantation. Transplanted fetal cardiomyocytes were examined for survival by immunostaining with anti-rat artial natriuretic peptide (ANP) and anti-CTLA4-Ig antibodies.Results. X-gal staining and immunostaining showed infection to be approximately 30% at 10 MOI, 65% at MOI 50, and 50〜70% at MOI>100, 3 days after infection with AdCTLA or AdRL.The cardiomyocytes infected with AdCTLA expressed CTLA4-Ig and survived to 8 weeks after xenotransplantation in all of these mice. However, cardiomyocytes infected with AdRL and non-infected cells were not detected even 2 weeks after xenotransplantation.Conclusion. Fetal cardiomyocytes were successfully infected by AdCTLA and AdRL.Survival of xenografted fetal cardiomyocytes is prolonged by adenovirus-mediated CTLA4-Ig expression.