[Show abstract][Hide abstract] ABSTRACT: Embryonic stem cell-derived cardiomyocytes are a useful source for cell transplantation into the heart, as well as for tissue engineering of the extracardiac vascular system. The present study was designed to investigate the survival and contractile function of embryonic stem cell-derived cardiomyocytes around large blood vessels to assess the feasibility of their ectopic use for future engineering of cardiovascular tissues.
The mouse embryonic stem cell-derived cardiomyocytes were transplanted into the retroperitoneum of the adult nude mice, and the myocardial tissues that developed were characterized by electrophysiological and histological techniques.
Macroscopic and electrophysiological analyses showed spontaneously contracting transplants in the host retroperitoneum 7 and 30 days after transplantation. Immunohistochemistry detected developing cardiomyocytes in the transplants on Day 7, which formed the myocardial tissues. They were positive for cardiac troponin I, cadherin, connexin 43, and proliferating cell nuclear antigen, but negative for alpha-smooth muscle actin. Vascular formation was discernible in the transplant tissues. By Day 30, more mature myocardial tissues had been established in the transplants. Electron microscopic study emphasized that the transplant tissues comprised cardiomyocytes, in which myofibrils with organized sarcomeres were observed. Desmosomes, fasciae adherens and gap junctions were evident in the cellular junctions.
The cardiomyocytes derived from the mouse ES cells were demonstrated to be viable and function in the ectopic site of the host retroperitoneum up to Day 30, following a process of proliferation and differentiation. Vascularization and host perfusion beneficial for the survival of the cardiomyocytes occurred in the transplants.
Cardiovascular Research 06/2003; 58(2):435-43. DOI:10.1016/S0008-6363(02)00730-7 · 5.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In spite of the fact that patients with heart diseases requiring heart transplantation are increasing in the world, there are a lack of donors, which makes it hard to offer them these life-saving transplants. As a way to overcome this dilemma, we have researched the addition of the new biopump, which consists of the cultured embryonic cardiomyocytes grafted around the abdominal aorta and contracts spontaneously, which subsequently supports the function of the host heart. Ventricular tissues from ICR 14-day-old embryos were cultured and were injected to BALB/c nude mice (male, 8-week-old) subperitoneally around the abdominal aorta. At 3 and 7 days after implantation, action potential of the grafts was measured. Grafts were prepared for histological study. The grafts survived, showed vigorous angiogenesis, and contracted spontaneously. The cardiomyocytes in the grafts showed irregular arrangement, containing myofibrils with sarcomeres and intercalated disks. It was confirmed by immunohistochemistry that the cardiomyocytes in the grafts matured in accordance with normal development. The grafts were very quickly invaded by small vessels from the surrounding tissues showing the formation of new circulation. Embryonic cardiomyocytes have the ability to remodel the abdominal aorta into a spontaneous pulsating apparatus and to function as a vascular pump.