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J Thorac Cardiovasc Surg 2001;121:932-942
© 2001 The American Association for Thoracic Surgery
Surgery for Acquired Cardiovascular Disease |
From the Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
R.K.L. is a Research Scholar of the Heart and Stroke Foundation of Canada. This research was supported by R.K.L.'s research grant from The Hospital for Sick Children Foundation (XG 98-063).
Received for publication May 4, 2000. Revisions requested Oct 25, 2000; revisions received Dec 4, 2000. Accepted for publication Dec 7, 2000. Address for reprints: Ren-Ke Li, MD, PhD, Toronto General Hospital, CCRW 1-815, 101 College St, Toronto, Ontario, Canada M5G 2C4 (E-mail: RenKe.Li{at}UHN.on.ca).
Objective: The synthetic materials currently available for the repair of cardiac defects are nonviable, do not grow as the child develops, and do not contract synchronously with the heart. We developed a beating patch by seeding fetal cardiomyocytes in a biodegradable scaffold in vitro. The seeded patches survived in the right ventricular outflow tract of adult rats.
Methods: Cultured fetal or adult rat heart cells (1 x 106 cells) were seeded into a gelatin sponge (15 x 15 x 1 mm), and the cell number was expanded in culture for 1 or 3 weeks, respectively. The free wall of the right ventricular outflow tract in syngeneic adult rats was resected and repaired with either unseeded patches or patches seeded with either fetal or adult cardiomyocytes (n = 10 for each group). The patches were examined histologically over a 12-week period.
Results: A significant inflammatory reaction was noted in the patch at 4 weeks as the scaffold dissolved. At 12 weeks, the gelatin scaffold had completely dissolved. Both types of the seeded cells were detected in the patch with 5-bromo-2'-deoxyuridine staining, and they maintained their continuity. Unseeded patches had an ingrowth of fibrous tissue. The patches became thinner between the fourth and the twelfth weeks in unseeded (P = .003), fetal (P = .0001), and adult (P = .07) cardiomyocyte groups as the scaffold dissolved. The control patch, but not the cell-seeded patches, was thinner than the normal right ventricular outflow tract. The endocardial surface area of each patch was covered with endothelial cells identified by factor VIII staining.
Conclusions: A gelatin patch was used to replace the right ventricular outflow tract in syngeneic rats. The seeded cells survived in the right ventricular outflow tract after the scaffold dissolved 12 weeks after implantation. In addition, the unseeded patches encouraged the ingrowth of fibrous tissue as the scaffold dissolved and the patches remained completely endothelialized.
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