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J Thorac Cardiovasc Surg 1997;113:10-018
© 1997 Mosby, Inc.

CARDIAC AND PULMONARY REPLACEMENT

TRANSPLANTATION OF GENETICALLY MARKED CARDIAC MUSCLE CELLS

Supported in part by a grant from the Ministry of Health and Welfare, Tokyo, Japan.

Received for publication Nov. 17, 1995 Revisions requested Feb. 22, 1996 Revisions received April 17, 1996 Accepted for publication April 25, 1996 Address for reprints: Satoshi Gojo, MD, Department of Surgery III, Nara Medical College, 840 Shijo-cho, Kashihara, Nara 634, Japan.

Abstract

We examined the possibility that cardiomyocytes could be genetically marked or modified before being grafted to the heart under conditions applicable to the clinical setting. We used a replication-defective recombinant adenovirus carrying the ß-galactosidase reporter gene, and delivered it to cultured murine fetal cardiac myocytes. Virtually all fetal cardiomyocytes in a primary culture expressed ß-galactosidase 24 hours after recombinant adenovirus infection. These cells were transplanted to the hearts of syngenic adult recipient mice. Expression of the ß-galactosidase gene in the grafted cells was demonstrated by staining with 5-bromo-4-chloro-3-indoyl-ß-D-galactosidase, resulting in a blue color at the histochemical level and an electron-dense deposit on transmission electron microscopic analysis. Gene expression was recognized from 7 days to 12 weeks after transplantation. Implanted cardiomyocytes aligned themselves along the layers of the host myocardium. Formation of gap junctions was demonstrated by transmission electron microscopy. Neither inflammation nor fibrous scar tissue was detectable by histologic analysis. This study demonstrates that ex vivo gene transfer to the heart by means of the adenoviral vector is possible.

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