Cord blood hematopoietic stem cell transplantation

Abstract

Umbilical cord blood (CB) is a clinically useful source of hematopoietic stem (HSC) and progenitor (HPC) cells for treatment of a wide variety of malignant and non-malignant disorders. Amongst the benefits of CB, compared to bone marrow (BM) and mobilized peripheral blood (MPB), as a source of engrafting HSC and HPC are its ready availability through CB banks, and a relatively low level of graft vs. host disease (GVHD) elicited after transplantation. Disadvantages of CB, compared to BM and MPB, include the low, and sometimes limiting, number of cells collected in single donor units which can be less than optimal for engraftment of many adults and higher weight children, and the relatively slower speed to engraftment of neutrophils and platelets. While limiting numbers of nucleated cells found in single units of CB can be compensated for by transplantation of more than 1 unit of CB, this use of multiple cord blood units may be associated with increased GVHD, and has not meaningfully reduced the time to neutrophil and platelet engraftment. Thus, means to enhance numbers and/or potency of collected cells and their engrafting capability through ex-vivo and/or in-vivo maneuvers would likely enhance the efficacy and applicability of CB transplantation. Such efforts require a deeper understanding of the cell biology of HSC and HPC, the microenvironment that nurtures these cells, and greater mechanistic insight into cell surface receptors and intracellular signaling pathways regulating HSC/HPC function. This information could provide the means to modulate these cells for greater clinical advantage. There is also the potential, as yet far from proven in a clinical sense for use of mature cells generated from HSC/HPC, and for non-HSC/HPC uses of CB. Non-HSC/HPC include mesenchymal stem/stromal cells (MSC), endothelial progenitor cells (EPC), and induced pluripotent stem cells (iPSC). Caution is clearly required for non HSC/HPC stem/progenitor cell uses of CB, based on insufficient biological and preclinical information for MSC, EPC, and iPSC. This review addresses current knowledge and potential future means to enhance the quantity, quality and/or engrafting activity of CB HSC/HPC, and where the field stands in context of MSC, EPC, and iPSC from CB.