Abstract:
BACKGROUND:Prolonged survival of xenografted neonatal cardiomyocytes was achieved by blocking the CD28/B7 costimulatory pathway via CTLA4-Ig gene transfer. We examined the long-term survival of xenografted neonatal cardiomyocytes by adenovirus-mediated CTLA4-Ig expression and transient CD40 blockade with anti-CD40L monoclonal antibody (MR1). METHODS AND RESULTS:Neonatal cardiomyocytes derived from Dark Agouti rats were infected with CTLA4-Ig-expressing adenovirus vectors and injected directly into the normal myocardium of C3H/He mice. Mice were also given an intraperitoneal injection of 500 microg MR1 (CTLA+MR group, n=30) or control immunoglobulin (CTLA group, n=30) 1 hour before and 1, 3, and 7 days after cardiomyocyte implantation. As a control, cells infected with beta-Gal-expressing adenovirus vector (RL group, n=15) and cells without infection (control group, n=15) were injected into additional mice. Mice from all groups were killed 2, 4, and 8 weeks after xenotransplantation, and mice from the CTLA+MR and CTLA groups were killed 4 and 6 months after xenotransplantation. Neonatal cardiomyocytes were successfully infected by adenovirus vectors. Immunohistochemical analysis showed that the xenografted cardiomyocytes survived and expressed CTLA4-Ig for 6 months in all mice from the CTLA+MR and CTLA groups. A gap junction between the xenografted and host cardiomyocytes was also confirmed. Conversely, neonatal cardiomyocytes did not survive for even 2 weeks after xenotransplantation in the mice from the RL and control groups. CONCLUSIONS:Long-term survival of xenografted neonatal cardiomyocytes was achieved by adenovirus-mediated CTLA4-Ig expression and transient CD40 blockade.
journal_name
Circulationjournal_title
Circulationauthors
Li TS,Ito H,Kajiwara K,Hamano Kdoi
10.1161/01.CIR.0000091086.54107.49subject
Has Abstractpub_date
2003-10-07 00:00:00pages
1760-5issue
14eissn
0009-7322issn
1524-4539pii
01.CIR.0000091086.54107.49journal_volume
108pub_type
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