This Article Full Text Full Text (PDF) All Versions of this Article: 108/14/1760    most recent 01.CIR.0000091086.54107.49v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, T.-S. Articles by Hamano, K. Search for Related Content PubMed PubMed Citation Articles by Li, T.-S. Articles by Hamano, K. Pubmed/NCBI databases Substance via MeSH Related Collections Transplantation

(Circulation. 2003;108:1760.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Long-Term Survival of Xenografted Neonatal Cardiomyocytes by Adenovirus-Mediated CTLA4-Ig Expression and CD40 Blockade

From the Division of Cardiovascular Surgery, Department of Medical Bioregulation (T.-S.L., H.I., K.H.), and the Department of Neurosurgery (K.K.), Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.

Correspondence to Kimikazu Hamano, MD, PhD, Division of Cardiovascular Surgery, Department of Medical Bioregulation, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, Japan 755-8505.

Received February 12, 2003; de novo received April 8, 2003; revision received June 4, 2003; accepted June 13, 2003.

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 µg 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 ß-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.

Key Words: myocardium • transplantation • survival

This article has been cited by other articles:

				T.-S. Li, M. Hayashi, H. Ito, A. Furutani, T. Murata, M. Matsuzaki, and K. Hamano Regeneration of Infarcted Myocardium by Intramyocardial Implantation of Ex Vivo Transforming Growth Factor-{beta}-Preprogrammed Bone Marrow Stem Cells Circulation, May 17, 2005; 111(19): 2438 - 2445. [Abstract] [Full Text] [PDF]