Cardiomyocyte progenitor cell-derived exosomes stimulate migration of endothelial cells.

Patients suffering from heart failure as a result of myocardial infarction are in need of heart transplantation. Unfortunately the number of donor hearts is very low and therefore new therapies are subject of investigation. Cell transplantation therapy upon myocardial infarction is a very promising strategy to replace the dead myocardium with viable cardiomyocytes, smooth muscle cells and endothelial cells, thereby reducing scarring and improving cardiac performance. Despite promising results, resulting in reduced infarct size and improved cardiac function on short term, only a few cells survive the ischemic milieu and are retained in the heart, thereby minimizing long-term effects. Although new capillaries and cardiomyocytes are formed around the infarcted area, only a small percentage of the transplanted cells can be detected months after myocardial infarction. This suggests the stimulation of an endogenous regenerative capacity of the heart upon cell transplantation, resulting from release of growth factor, cytokine and other paracrine molecules by the progenitor cells--the so-called paracrine hypothesis. Here, we focus on a relative new component of paracrine signalling, i.e. exosomes. We are interested in the release and function of exosomes derived from cardiac progenitor cells and studied their effects on the migratory capacity of endothelial cells.

Routing of the aquaporin-2 water channel in health and disease.

The identification of the first water channel in 1991 opened up a new field in cell biology and physiology that significantly increased our understanding of mammalian water balance regulation. Since then, nine other mammalian aquaporins have been identified. Although the physiological significance of many aquaporins is still to be elucidated, it has been clearly established for aquaporin-2. This water channel, which is expressed in the renal collecting duct, is redistributed to the apical membrane in response to a intracellular signaling cascade, initiated by binding of the antidiuretic hormone vasopressin to its receptor. In pathological conditions, characterized by a reduced reabsorption of water from urine, the expression of aquaporin-2 and the apical targeting is always found to be reduced or absent. Naturally-occurring AQP2 mutations that cause Nephrogenic Diabetes Insipidus, a disease in which the kidney is unable to concentrate urine in response to vasopressin, are extreme examples of this condition. In contrast, in diseases with increased renal water uptake, total and apical membrane expression of aquaporin-2 is increased. Since most aquaporins, including aquaporin-2, are considered to be constitutively open channels, much attention has been given to the regulation of the shuttling of aquaporin-2 to the apical membrane. This review focusses on the present understanding of the regulation of the routing of aquaporin-2 in collecting duct cells and the misrouting of aquaporin-2 mutants in Nephrogenic Diabetes Insipidus.