Engineering Robust and Functional Vascular Networks in Vivo with Human Adult and Cord Blood-Derived Progenitor Cells

摘要

The success of therapeutic vascularization and tissue engineering (TE) will rely on our ability to create vascular networks using human cells that can be obtained readily, expanded safely ex vivo and produce robust vasculogenic activity in vivo. We hypothesized that blood derived endothelial progenitor cells (EPCs) have the required proliferative and vasculogenic activity to create vascular networks in vivo. To test this, EPCs were isolated and expanded from human umbilical cord blood or from adult peripheral blood. EPCs were then combined with human saphenous vein smooth muscle cells (HSVSMCs) as a source of perivascular cells, suspended in Matrigel and implanted subcutaneously into immunodeficient mice. Evaluation of implants at one week revealed an extensive network of human-specific lumenal structures containing erythrocytes, indicating formation of functional anastomoses with the host vasculature. This study demonstrated that human blood-derived EPCs were able to form the endothelial lining of vascular networks in vivo (Melero-Martin et al. 2007). To obtain a blood-derived progenitor cell that could perform the role of the mature smooth muscle cells, we isolated, expanded and characterized human mesenchymal progenitor cells (MPCs) from umbilical cord blood and from adult human bone marrow. We showed that MPCs differentiated towards a smooth muscle cell phenotype in vitro when co-cultured with EPCs, indicating the MPCs had the appropriate differentiation potential to substitute for mature smooth muscle cells. Indeed, we found that EPCs combined with MPCs formed robust, extensive vascular networks in vivo in the Matrigel model described above(Melero-Martin et al. 2008). The rapid formation of long-lasting microvascular networks by human post-natal progenitor cells, the EPCs and MPCs, constitutes an important step in the development of clinical strategies for tissue vascularization.