Cord Blood Stem Cell Expansion Ex Vivo With Endothelial Progenitor Cells

DESCRIPTION (provided by applicant): Bone marrow transplantation is an effective means to treat patients with inherited or acquired defects in blood formation. However, only 1/3 of the potential recipients can find suitable donor grafts. Human umbilical cord blood contains sufficient hematopoietic stem (HSC) and progenitor cells to engraft related recipients (even adults). A limitation to more widespread use of cord blood as a donor graft for adult patients is that cord blood units may not contain sufficient numbers of HSC in situations where the recipient is unrelated and/or HLA mismatched. Identification of methods to expand cord blood HSC would have significant clinical applications and constitute a significant commercial market. We have recently identified a hierarchy of human endothelial progenitor cells that are present in the circulation of the human infant and adult and also reside in human arteries and veins. In preliminary studies, we have co-cultured umbilical cord blood HSC (CD34+CD38- enriched by flow cytometry) with cord blood-derived endothelial progenitor cells for 7 days ex vivo (with added hematopoietic growth factors) and demonstrated a > 100 fold increase in human CD45+ cell engraftment in the bone marrow of sublethally irradiated immunodeficient mice. In this Phase 1 grant we aim to 1) determine the fold expansion of human HSC using limiting dilution analysis experiments in immunodeficient mice to determine feasibility of using the endothelial progenitors to expand HSC ex vivo and 2) will also determine whether the HSC expansion can occur in a non-contact co-culture system.