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Ann Thorac Surg 1996;62:660-661
© 1996 The Society of Thoracic Surgeons
DR CLIFFORD H. VAN METER (New Orleans, LA): I noticed that on electron microscopy, you could demonstrate intercalated discs between the transplanted cells. Were you able to identify adherence junctions or nascent discs or any other structure between the transplanted cells and the host cells?
DR LI: We did not evaluate whether the transplanted fetal cells communicated with the recipient heart cells because the histologic studies demonstrated that transplanted cardiac tissue was surrounded by the myocardial scar tissue.
DR VAN METER: Were ultrasonic microcrystals used to detect the shortening fractions? If so, were they left in place on the organ after transplantation for some period, or were they replaced at an interval after transplantation?
DR LI: We used echocardiography rather than ultrasonic crystals to evaluate the function of the transplanted cardiac tissue. In a previous study [1], we transplanted fetal rat cardiomyocytes into the subcutaneous fibrous tissue of the adult rat leg. On days 14 and 21 after transplantation, echocardiography was performed at the transplant sites to evaluate the function of the transplanted cardiac tissue.
DR VAN METER: Have you measured action potentials at the transplanted sites?
DR LI: Yes. We found that the transplanted tissue had a distinct idioventricular electrocardiogram that corresponded to the contraction of the cardiac tissue.
DR JAMES K. KIRKLIN (Birmingham, AL): First, it was not clear to me from your presentation whether this was an allogeneic or syngeneic model. If allogeneic, did you see evidence of rejection in the myocyte transplants? Second, I take it these were fetal myocytes because they were easier to grow in tissue culture. If that is true, how do you hypothesize this would be used clinically in adults? What would be the source of myocytes for somebody after an acute myocardial infarction?
DR LI: We used allogeneic rats in this study. Lymphocyte infiltration occurred around the cardiac tissue formed by transplanted fetal cardiomyocytes despite daily administration of cyclosporin A. However, the transplanted cells formed cardiac tissue, survived in the myocardial scar tissue, and improved the function of the scarred hearts. The cyclosporin A may have delayed the rejection of the allogeneic fetal rat heart cells.
The clinical application of cardiomyocyte transplantation can be envisioned in three clinical scenarios. Cardiomyocytes can be transplanted (1) into freshly infarcted myocardium to reduce scar formation and (2) into myocardial scar tissue before aneurysm formation to limit scar expansion. Also, (3) in patients with an established aneurysm, transplanted cells can be seeded onto a pericardial patch used to replace the myocardial scar tissue.
Cardiomyocytes for cell transplantation could be obtained from animals, fetal human hearts, or adult human heart biopsy specimens. A number of research groups are investigating the feasibility of transplanting genetically engineered pig hearts into humans. Genetically engineered pig fetal cardiomyocytes could be transplanted into human myocardial scar tissue. Human fetal cardiomyocytes could be another source for cell transplantation. Although this approach is controversial, some research groups currently use human fetal cells for transplantation into the human brain to treat Parkinson's disease. A human fetal cell line could be established and cells frozen for storage. In this way, one fetal heart could be used for transplantation into several patients. Cardiomyocytes could be obtained from the patient's own heart and cultured for subsequent transplantation into his or her own myocardium. Autotransplantation would be ideal because it would avoid rejection.
DR CRAIG R. SMITH (New York, NY): One would still expect this scar to be severely ischemic, yet you have been able to show functioning muscle in this region. From where do you think it is getting its blood supply?
DR LI: Using immunohistochemical technique, we have identified blood vessels in the cardiac tissue formed by the transplanted cardiomyocyte suspension. The blood vessel density in the transplanted cardiac tissue was significantly greater than that in myocardial scar tissue. This observation was confirmed by electron microscopy.
DR VAN METER: I do not mean to belabor this, but in our research laboratory, we have in fact used human fetal heart cells from a therapeutic pregnancy termination and successfully transplanted them into the pig. The angiogenesis may be the end result of this rather than the proliferation of the cells. We have not determined what this angiogenic influence is. Concurrently with the cellular implants, we are injecting microspheres with vascular endothelial growth factor and fibroblast growth factor to see if the neovascularization can be accomplished without the cells. We would like to see no inflammatory response so that it is not implicated as the cause of the neovascularization. However, I think your work is outstanding and applaud you for it.
Reference
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