Figure 6: Regulatory mechanisms controlling angiogenesis by multipotent MSCs and mature ECs. To regulate their overall activities, cells use a variety of clearly-defined environmental signals differentially associated with ON (black arrows) and OFF (red arrows) mechanisms, which stimulate and inhibit intracellular effectors respectively. Our results from UCBMSCs indicate that response to angiogenic stimuli is controlled by a central PKC/MAPK/ERK/Egr-3 signaling clue. In Matrigel, UCBMSCs form well-developed networks resembling last stages of in vivo angiogenesis in which they also participate actively, as we have previously demonstrated in mice where new microvasculature connected with the host circulatory system are developed [18]. We also suggest that there are mechanisms unique to mature ECs (discontinuous lines) and common (continuous lines) to multipotent MSCs and ECs regulating angiogenesis.