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J Thorac Cardiovasc Surg 2000;119:368-375
© 2000 Mosby, Inc.
SURGERY FOR CONGENITAL HEART DISEASE |
From the Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Supported by research grants to R.K.L. from the Medical Research Council of Canada (MT-13665) and The Hospital for Sick Children Foundation (XG 98-063). R.K.L. is a Research Scholar of the Heart and Stroke Foundation of Canada. R.D.W. is a Career Investigator of the Heart and Stroke Foundation of Ontario. The authors are working in partnership with Genzyme Corp.
Address for reprints: Ren-Ke Li, MD, PhD, Toronto General Hospital, CCRW 1-815, 200 Elizabeth St, Toronto, Ontario, M5G 2C4 Canada (E-mail: Renki.Li{at}uhn.on.ca).
Objectives: Currently available graft materials for repair of congenital heart defects cause significant morbidity and mortality because of their lack of growth potential. An autologous cell-seeded graft may improve patient outcomes. We report our initial experience with the construction of a biodegradable graft seeded with cultured rat or human cells and identify their 3-dimensional growth characteristics.
Methods: Fetal rat ventricular cardiomyocytes, stomach smooth muscle cells, skin fibroblasts, and adult human atrial and ventricular cardiomyocytes were isolated and cultured in vitro. These cells were injected into or laid onto biodegradable gelatin meshes, and their rate of proliferation and spatial location within the mesh was evaluated by using a cell counter and histologic analysis.
Results: Rat cardiomyocytes, smooth muscle cells, and fibroblasts demonstrated steady proliferation over 3 to 4 weeks. The gelatin mesh was slowly degraded, but this process was most rapid after seeding with fibroblasts. Human atrial cardiomyocytes proliferated within the gelatin meshes but at a slower rate than that of fetal rat cardiomyocytes. Human ventricular cardiomyocytes survived within the gelatin mesh matrix but did not increase in number during the 2-week duration of evaluation. Grafts seeded with rat ventricular cells exhibited spontaneous rhythmic contractility. All cell types preferentially migrated to the uppermost surface of each graft and formed a 300- to 500-µm thick layer.
Conclusions: Fetal rat ventricular cardiomyocytes, gastric smooth muscle cells, skin fibroblasts, and adult human atrial cardiomyocytes can grow in a 3-dimensional pattern within a biodegradable gelatin mesh. Similar autologous cell-seeded constructs may eventually be applied to repair congenital heart defects.
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