Expansion and Homing of Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells for Clinical Transplantation

Abstract

The successful expansion of hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood (UCB) for transplantation could revolutionize clinical practice by improving transplantation-related outcomes and making available UCB units that have suboptimal cell doses for transplantation. New cytokine combinations appear able to promote HSPC growth with minimal differentiation into mature precursors and new agents, such as insulin-like growth factor-binding protein 2, are being used in clinical trials. Molecules that simulate the HSPC niche, such as Notch ligand, have also shown promise. Further improvements have been made with the use of mesenchymal stromal cells, which have made possible UCB expansion without a potentially deleterious prior CD34/CD133 cell selection step. Chemical molecules, such as copper chelators, nicotinamide, and aryl hydrocarbon antagonists, have shown excellent outcomes in clinical studies. The use of bioreactors could further add to HSPC studies in future. Drugs that could improve HSPC homing also appear to have potential in improving engraftment times in UCB transplantation. Technologies to expand HSPC from UCB and to enhance the homing of these cells appear to have attained the goal of accelerating hematopoietic recovery. Further discoveries and clinical studies are likely to make the goal of true HSPC expansion a reality for many applications in future.

Umbilical cord blood-derived non-hematopoietic stem cells retrieved and expanded on bone marrow-derived extracellular matrix display pluripotent characteristics

“…To further assess the quality and variation of the UCB samples, we also examined the expression of CD34, a HSC marker. In the current study, the percentage of CD34-positive cells in the UCB MNCs was fairly low (range, 0 to 20%; median, 2.2%), but in the range previously reported for HSCs from peripheral blood and BM [35, 36]. …”

Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation

“…5 Current studies to enhance clinical UCB transplantation outcomes have focused on expanding UCB HSPC ex vivo and/or improving their BM homing. 2,3,6 Erythropoietin (EPO) affects the fate of hematopoietic progenitor cells (HPCs) in favor of erythroid differentiation. 7 In addition, circulating HPCs rapidly decline after birth, 8,9 which has been shown to coincide with a decrease in EPO blood concentration.…”

Mesenchymal Stem Cell Derived Extracellular Vesicles: A Role in Hematopoietic Transplantation?

“…On the contrary, other studies have demonstrated that the co-infusion of MSCs at the time of UCB transplantation has no effect on the kinetics of engraftment and on the prevention of GvHD [52], inhibits thymic reconstitution, and has a negative effect on patient’s survival [53]. MSCs have been also employed to stimulate ex vivo UCB-derived HSC allowed to obtain a great number of total nucleated cells and hematopoietic progenitor cells [54,55]. In a clinical trial conducted on 31 patients receiving two different units of UCBsc, one of which expanded ex vivo with MSCs, a significant improvement of early UCBsc engraftment with respect to the infusion of the un-manipulated UCBsc unit only was shown.…”