Strategies for generating human tissues for regenerative medicine have recently been boosted by the development of novel stem cell technologies. However, current technologies are not exempt of risk and require further optimization for their safe application in humans. During the course of this project we have been able to identify novel genetic elements and laboratory conditions facilitating the conversion of human skin cells to vessels comprising the vascular system. The generation of vessels in the laboratory may allow for the treatment of multiple human maladies including ischemic situations, vascular defects and other diseases affecting the cardiovascular system, which collectively, remain the major cause of mortality in the developed world. Our methodologies increased the overall efficiency (by shortening the time required to generate vessels and increasing the amount of cells yielded), and thus future availability for patients, as well as demonstrated a safer profile when compared to previous technologies.