Umbilical cord blood-derived endothelial progenitor cells for cardiovascular tissue engineering

Abstract

Term and preterm human umbilical cord blood (UCB) represents an easily accessible autologous and allogeneic cell source of hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), and endothelial colony forming cells (ECFCs, or alternatively outgrowing endothelial cells, OECs). All three cell types are regarded as valuable sources for regenerative medicine for pre- or postnatal therapies. In this section we would like to focus on endothelial progenitor cells (EPCs) used for cardiovascular tissue engineering purposes and ECFCs as example to investigate standardized chemically defined cell-culture protocols. Various cells originally identified as EPCs presented in various studies were and are in fact mostly hematopoietic cells (CD45+ progenitor cells, monocytes, platelets) that display angiogenic properties but are clearly distinct to rare circulating ECFCs or OECs (CD31+, CD34+, CD105+, CD146+, but 45-), since only ECFCs have the potential (in contrast to EPCs) of postnatal vasculogenic activity upon transplantation in a matrix scaffold. Because several different types of blood-derived endothelial cells are implicated as pro-angiogenic, future studies will be required to determine the exact role that each endothelial cell type plays in the process of vascular repair or regeneration. Up until now little is known of the in vivo functions of ECFCs in the many preclinical models of human cardiovascular disease and increased studies in this area may be illuminating. Recent studies revealed that infusion of ECFCs into pigs following experimentally induced acute myocardial infarction resulted in significant improvement in myocardial infarct remodeling and heart function via direct incorporation of the cells into the host endothelium. Also studies in murine models of retinal ischaemia showed that human ECFCs directly incorporate into the host murine vasculature, significantly decreasing avascular areas, concomitantly increasing normo-vascular areas and preventing pathologic pre-retinal neovascularization. In the field of cardiovascular regeneration and tissue engineering the endothelialization of constructs before implantation represents a crucial element of the fabrication process of potential implants to ensure lack of thrombogenicity in vivo. Therefore, UCB-EPCs have been intensively investigated in several in vitro studies for the fabrication of tissue engineered patches, vascular grafts and heart valves showing promising initial results. In vitro, the seeded UCB-EPCs showed a stable phenotype during static conditioning and the functionality of the cells was similar to mature vascular-derived endothelial cells. However, prior to a clinical translation of the concept, careful preclinical in vivo assessment of the UCB-EPC-based concept seems indispensable.