Vessels provide the conduits that deliver metabolites and oxygen to the tissue and export waste products. After ischemia or tissue injury, endothelial cells migrate and proliferate to re-establish the capillary network in a process termed angiogenesis to maintain oxygen supply. Besides these essential and well-established functions in oxygen delivery, recent studies suggest that endothelial cells contribute to the multicellular-crosstalk that balances regeneration and dysfunctional or maladaptive healing. Thus, endothelial cells not only seem important for oxygen delivery but act as paracrine source for signals that determine tissue regeneration versus fibrosis. The interaction of endothelial-derived signals with hepatocyte functions has already been shown in the development of model organisms such as zebrafish1 and more recently during regeneration of lung and liver in adult mice.