Transplantation of Endothelial Progenitor Cells Solely Leads to Development of Functional Neo-vessels in vivo.
It has been believed that de novo vessel formation (neo-vasculogenesis) can be induced by co-transplantation of pericytes or mesenchymal stem/progenitor cells (MSPC) with endothelial cells or endothelial colony-forming cells (ECFC). The requirement for co-transplantation of two adult progenitor cells is one factor that can potentially complicate the process of therapeutic vasculogenesis which hampers the development of strategies for therapeutic intervention referred to as regenerative medicine. Here we employed a novel strategy for therapeutic vessel development by transplanting endothelial colony forming progenitor cells solely to immune compromised mice and detect vessel formation capacity of single ECFC transplants compared to ECFC/MSPC co-transplants. We applied umbilical cord derived and bone marrow derived-MSPC and umbilical cord derived ECFC with different total cell number for subcutaneous transplantation in matrix composites either alone or mixed at a ratio of 1:5 subcutaneously into immune deficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ; NSG mice. Implants were harvested one day, one, two, eight and 24 weeks after transplantation for detecting the state of vessel formation and stability of the transplants by histological assessments. Additionally, endothelial progenitor cells derived from various human tissues such as umbilical cord blood, peripheral blood and white adipose tissue were used to assess their potential for vessel formation in vivo.\n\nResults confirmed that single transplantation of ECFCs with a higher cell number and later in the time course after transplantation is as efficient as co-transplantation of ECFC with MSPC at forming stable-perfused human vessels. Amongst ECFCs isolated from different human sources, white adipose tissue derived ECFC are most potent in forming neo-vessels (micro-vessels) in vivo, thus WAT-ECFC could be an optimal cell for vasculogenesis regenerative application.\n\nCo-transplantation of ECFC and MSPC with the defined 5:1 ratio or sole ECFC with a higher cell dosage was essential for vessel generation in vivo.