Prolonged survival of xenograft fetal cardiomyocytes by adenovirus-mediated CTLA4-Ig expression.
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 costimulatory pathway via CTLA4-Ig gene transfer.


METHODS
Fetal cardiomyocytes derived from Dark Agouti 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 beta-Gal-expressing adenovirus vector (AdRL) and cells without infection were injected into additional mice (n=30). 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 atrial natriuretic peptide and anti-CTLA4-Ig antibodies.


RESULTS
Fetal cardiomyocytes were successfully infected by AdCTLA and 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 noninfected cells were not detected even 2 weeks after xenotransplantation.


CONCLUSIONS
Survival of xenografted fetal cardiomyocytes is prolonged by adenovirus-mediated CTLA4-Ig expression.
Li
T S
TS
First Department of Surgery, Yamaguchi University School of Medicine, Ube, Japan.
Hamano
K
K
Kajiwara
K
K
Nishida
M
M
Zempo
N
N
Esato
K
K
D000069594:Abatacept; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology*; D060908:CTLA-4 Antigen; D017690:Cell Transplantation; D005333:Fetus / Q000502:physiology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006085:Graft Survival / Q000187:drug effects*; D018796:Immunoconjugates; D051379:Mice; D008809:Mice, Inbred C3H; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014183:Transplantation, Heterologous
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; C556708:Ctla4 protein, rat; D018796:Immunoconjugates; D000069594:Abatacept