Image-guided intramyocardial cell injection: putting a puzzle piece in the right place

Despite significant advances in the management of acute myocardial infarction, it remains a major cause of morbidity and mortality. After myocardial infarction, viable myocardi-um is lost and is replaced by fibrotic tissue. This increases the tensile strength of the infarcted myocardium preventing cardiac rupture. However, ultimately it impairs the contractile capacity of the heart leading to heart failure. For several years, cell transplantation has been employed in the damaged heart of patients with end-stage heart failure. The aim of cell transplantation is to improve cardiac function. Indeed, to this point clinical trials show a modest therapeutic effect of cardiac cell therapy on cardiac function. The positive effects of cell therapy are believed to be mainly mediated by paracrine factors excreted by the transplanted cells. The role of direct cardiomyogenic or angiogenic differentiation of the transplanted cells that have been used in the clinical trials is thought to be small. Furthermore, pre-clinical studies have shown that only low percentages of injected cells survive and engraft in the infarcted myocardium. This finding could explain the modest effects that have been observed in both pre-clinical and clinical studies. Several studies are therefore aiming to improve stem cell survival and engraftment (e.g. by using biomaterials). Besides improving cell survival and en-graftment, a better selection of the location of cell injection may also influence the therapeutic effect of such therapy. In the study by Van Slochteren et al. a 3D Cardbox image registration toolbox is used which makes it possible to stan-dardise the transplantation location.[1] In this study, the researchers aimed to transplant stem cells in the 50 % infarct transmurality border zone. It is expected that in this area the stem cells are able to exert their therapeutic effects, while not being deprived of oxygen and nutrients. Indeed, it is known that the physiological niche of bone marrow-derived mesen-chymal stem cells, frequently studied for cardiac cell therapy, has a low oxygen tension. Furthermore, several studies have shown that hypoxia enhanced the tissue regenerative potential of bone marrow-derived mesen-chymal stem cells.[2, 3] Injection of stem cells in the correct location is therefore of importance to obtain the maximum therapeutic effect, which makes the results of this study highly relevant. The positive effect of cell therapy is also thought to be dependent on cell-to-cell contact. In a recent study it was shown that gap junctional coupling, which is essential in electrochemical communication between cardiomyocytes, is also …