This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Google Scholar Google Scholar Articles by Li, R.-K. Articles by Yau, T. M. Search for Related Content PubMed PubMed Citation Articles by Li, R.-K. Articles by Yau, T. M. Related Collections Other Treatment CV surgery: other Pediatric and congenital heart disease, including cardiovascular surgery

(Circulation. 1999;100:II-63.)
© 1999 American Heart Association, Inc.

Surgery for Valvular Heart Disease

Survival and Function of Bioengineered Cardiac Grafts

Ren-Ke Li, MD, PhD; Zhi-Qiang Jia, MD; Richard D. Weisel, MD; Donald A. G. Mickle, MD; Angel Choi, MSc; Terrence M. Yau, MD, MSc

From the Division of Cardiovascular Surgery, The Toronto Hospital, Department of Surgery, University of Toronto, Canada.

Correspondence to Dr Ren-Ke Li, CCRW 1-815, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4 Canada. E-mail rli{at}torhosp.toronto.on.ca

Introduction—Patients with congenital heart disease frequently require graft material for repair of cardiac defects. However, currently available grafts lack growth potential and are noncontractile and thrombogenic. We have developed a viable cardiac graft that contracts spontaneously in tissue culture by seeding cells derived from fetal rat ventricular muscle into a biodegradable material. We report our investigations of the in vitro and in vivo survival and function of this bioengineered cardiac graft.

Methods and Results—A cardiomyocyte-enriched cell inoculum derived from fetal rat ventricular muscle was seeded into a piece of Gelfoam (Upjohn, Ontario, Canada), a biodegradable gelatin mesh, to form the graft. For in vitro studies, growth patterns of the cells within the graft were evaluated by constructing growth curves and by histologic examination; in in vivo studies, the graft was cultured for 7 days and then implanted either into the subcutaneous tissue of adult rat legs or onto myocardial scar tissue in a cryoinjured rat heart. Five weeks later, the graft was studied histologically. The inoculated cells attached to the gelatin mesh and grew in 3 dimensions in tissue culture, forming a beating cardiac graft. In both the subcutaneous tissue and the myocardial scar, blood vessels grew into the graft from the surrounding tissue. The graft implanted into the subcutaneous tissue contracted regularly and spontaneously. When implanted onto myocardial scar tissue, the cells within the graft survived and formed junctions with the recipient heart cells.

Conclusions—Fetal rat ventricular cells can grow 3-dimensionally in a gelatin mesh. The cells in the graft formed cardiac tissue and survived and contracted spontaneously both in tissue culture and after subcutaneous implantation. Future versions of this bioengineered cardiac graft may eventually be used to repair cardiac defects.

Key Words: heart defects, congenital • myocytes • myocardial infarction • myocardial contraction