Recent advances using stem cell‐derived cardiac and vascular cells for cardiomyoplasty

Abstract

Listen

Translate article

Stem cells of either adult or embryonic origin (embryonic stem cells, ES cells) are an unlimited source of cells that could be used for cell transplantation approaches to treat cardiac infarction and to overcome the shortage of donor organs. Whereas adult stem cell transplantation has already reached the clinical state, the research with ES cells is still in its infancy which is related to the danger of teratoma formation within the cell recipient as well as due to potential problems arising from immune responses towards the transplanted cells. Although some improvement in cardiac function has been observed so far using adult stem cell transplantation, the so far achieved benefit is not sufficient to allow routine patient treatment. Furthermore, the transdifferentiation of adult stem cells into cardiac cells that was reported in several studies could not be reproduced by other groups, and independent researchers reported that transdifferentiation was indeed a misinterpretation resulting from fusion of stem cells with adjacent cardiac cells. In contrast to adult stem cells the cardiovascular differentiation potential of ES cells is undoubted, and due to the huge proliferation capacity of ES cells this stem cell species may represent the most promising stem cell population that may be applied in future clinical approaches. However, besides problems of immune rejection which could be overcome with conventional immunosuppressants these cells bear the danger of teratoma formation which is arising from transplantation of still undifferentiated cells into the host organ. Several approaches have been elaborated during recent years to cope with teratoma generation. The most straightforward procedures to remove undifferentiated ES cells from preparations to be transplanted into organs are: antibiotic selection procedures, fluorescence‐activated cell sorting, differential centrifugation procedures, and cytotoxic antibodies directed against the undifferentiated cell population. One of the latest developments is the derivation of so called “induced ES cells”. These cells are gained by reprogramming somatic cells through introduction of stemness genes like Oct4, Sox2, Klf4, and c‐Myc. Upon transfection with these genes somatic cells achieve an ES cell phenotype and can be differentiated into cells of all three germ layers. Using induced ES cells immunological problems arising from allogeneic stem cell transplantation could be overcome since these stem cells are produced from the patients′ somatic cells thus carrying his immunological features. Besides scientific progress with the “classical” adult and ES cells, research of recent years came up with resident cardiac stem cells that reside in stem cell niches within the adult heart. It has been suggested that resident stem cells may be activated in situations of cardiac injury and may represent an intrinsic mechanism of cardiac repair, thus overcoming the previously generally accepted concept of the heart as a post‐mitotic organ. Currently researchers are trying to propagate resident cardiac stem cells in cell culture to scale up cell numbers for cell transplantation approaches. The transplantation procedures of stem cells are assisted by rapidly evolving tissue engineering procedures which utilize biodegradable scaffolds to fix transplanted cells within the transplantation site. Recent research has shown that successful engraftment of transplanted stem cell tissues into the infarcted heart can only be achieved if not only cardiomyocytes are transplanted into the area of infarction but additionally endothelial cells, smooth muscle cells and fibroblast ‐ which in concert built up the vascularized microenvironment that is necessary for cardiac cell proliferation and cell survival.