Cell Transplants for Ischemic Myocardium
Just a few years ago, the adult myocardium was thought to be incapable of regeneration. However, the rate of cell loss has proved to be such that, without cell replacement, most people would be heartless by the age of 40. To discover where the new cells come from, several groups have looked at sex-mismatched heart transplants. The presence of Y-chromosomes in the myocardium of a female heart transplanted into a man might suggest that certain cells originate outside the heart. One objection to some of the studies is that they do not allow for the microchimerism that can arise in a woman who has been pregnant with a male fetus. At the Berlin meeting, this objection was met in a biopsy study reported by Dr A. Bayes-Genis, from the Hospital Santa Crevi, Sant Pau, Barcelona, Spain. Muscle cells with two X-chromosomes were clearly evident in male hearts transplanted into females. Dr P. Muller and co-workers, from the Department of Internal Medicine, University of the Saarlandes, Homburg, Germany, have examined these cells and confirmed that they are cardiomyocytes connected by gap junctions to adjacent myocytes (Circulation. 2002;106:31–35). In the opinion of Dr M.L. Entman, from Baylor College of Medicine, Houston, Tex, all evidence points to a low-capacity system that has evolved for slow replacement of adult cardiac cells over a lifetime. How, then, might this process be sped up to aid the repair of damaged myocardium? At the meeting there was much debate on the potential value of bone marrow stem cells—mesenchymal, hematopoietic?— and also of skeletal myoblasts. The hope is that, if stem cells can be directed to newly damaged tissue, they will differentiate into myocytes rather than, say, fibrocytes. Dr B.E. Strauer, Heinrich Heine University, Düsseldorf, Germany, has reported the infusion of mononuclear bone marrow cells into the infarct-related coronary arteries of 10 patients with promising results (posted online before print September 3, 2002; DOI:10.1161/01.CIR.0000034046.87607.1C. Available at: http://www.circulationaha.org. Accessed September 10, 2002). As to skeletal myoblast autotransplantation, the latest work includes a phase 1 study by Dr T. Siminiak and others, from the University School of Medical Sciences, Poznan, Poland. Myoblasts were obtained from thigh muscle, cultured, and injected into the patient’s postinfarction scar (10 patients) during coronary artery bypass grafting. This group, too, is positive about the results: segmental contractility increased in previously akinetic areas. Commenting on this approach, Dr P. Menasché, from the Department of Cardiovascular Surgery, Hôspital Bichat Claude, Paris, France, declared the “proof of concept” established, but pointed out that, although myoblasts improve cardiac function, they never evolve into true cardiac cells; stem cells, on the other hand, might. Early experience with skeletal myoblasts indicates that arrhythmias may be troublesome.