Blood Outgrowth Endothelial Cells (BOEC) Developed in Xeno-Free Conditions for Ischemic Tissue Regeneration

Ischemic tissues that develop as a result of various types of injury, often lack oxygen and nutrients required for both structural and functional regeneration. Inducing the emergence of an adequate vasculature (revascularization) can improve blood flow; allowing essential nutrients to re-perfuse the injured tissue. Transplantation of endothelial cells, either alone or with other supporting cell types, are a promising approach for augmenting recovery.

Blood outgrowth endothelial cells (BOEC) are a potentially autologous, highly proliferative, and readily available endothelial cell source. BOEC have shown similar potency in degree of vascularization when compared to the clinically-restricted human umbilical vein endothelial cells (HUVEC) both in vitro and in vivo in the presence of adult adipose-derived mesenchymal stromal cells (adMSC). Previously, we described a young source of immunoprivileged pericyte-like MSC, first trimester human umbilical cord perivascular cells (FTM HUCPVCs), that supports angiogenesis both in vitro and in vivo. We have developed xeno-free culture conditions using cGMP-compliant human platelet lysate (HPL) that preserves the phenotype (CD31+, CD144+, CD105+, CD45-) and tube formation potential of BOEC in vitro. Our co-culture experiments have shown that, in vitro, BOEC and FTM HUCPVCs can interact on basal membrane extract (Matrigel^TM) to form tubes and endothelial cell sheets.

Our results suggest that clinically compatible angiogenic cell sources BOEC and FTM HUCPVC can be expanded in cGMP-compliant culture conditions for regenerative therapy after ischemic injury.