Abstract
BackgroundUmbilical cord blood (UCB) is becoming an alternative cell source for hematopoietic stem cell transplantation (HSCT). However, umbilical cord blood transplantation (UCBT) has been severely limited by low and finite numbers of hematopoietic stem cells and their delayed engraftment. New strategies are needed to improve ex vivo expansion efficiency and in vivo haematopoietic recovery.MethodsWe produced an endothelium-targeted soluble Notch ligand, the Delta-Serrate-Lag-2 (DSL) domain of human Delta-like 1 fused with a RGD motif (hD1R), and tested the effects of this protein on human umbilical cord blood hematopoietic stem and progenitor cell (UCB-HSPC) ex vivo and in vivo.ResultshD1R-mediated ex vivo expansion system was able to significantly increase the absolute number of UCB-HSPCs. The hD1R-expanded cells had the enhanced homing and maintained long-term hematopoietic stem cell repopulation capacity in the bone marrow of immunodeficient nonobese diabetic-severe combined immunodeficient (NOD/SCID) mice. Moreover, systemic administration of hD1R promoted the in vivo regeneration of donor cells in recipient mice and accelerated hematopoietic recovery, particularly in settings wherein the HSPCs dose was limiting.ConclusionsOur results indicated that hD1R might be applied in improving hematopoietic recovery and HSC engraftment in human UCBT.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0761-0) contains supplementary material, which is available to authorized users.
Highlights
Umbilical cord blood (UCB) is becoming an alternative cell source for hematopoietic stem cell trans‐ plantation (HSCT)
It should be noted that different conditions were tested: (1) Co-culture with human umbilical vein endothelial cell (HUVEC) supplemented with h5GF in the presence of PBS or hD1R; (2) Supernatant from HUVECs in the presence of h5GF plus hD1R; (3) Fixed HUVECs by 4 % PFA with h5GF plus hD1R
GSI effectively blocked Hes1 expression (Additional file 1: Figure S1C). These results suggested that live HUVECs were necessary for hD1R to activate Notch signaling
Summary
Umbilical cord blood (UCB) is becoming an alternative cell source for hematopoietic stem cell trans‐ plantation (HSCT). Umbilical cord blood transplantation (UCBT) has been severely limited by low and finite numbers of hematopoietic stem cells and their delayed engraftment. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is recognized as an effective treatment for patients with hematological and nonhematological malignancies. Umbilical cord blood (UCB) is becoming an alternative source of hematopoietic stem cells for patients requiring allo-HSCT when no suitable donors are available [1]. Many studies investigated the expansion of HSCs on mesenchymal progenitor, endothelial cell (EC) feeder layers, and CD146+ pericytes, which were used as surrogates for in vivo stem cell niches and provided necessary signaling cues to maintain the stemness of expanded cells [12,13,14]. Due to difference in the cytokines used and loss of long-term engraftable cells in vitro expansion, an effective protocol for the expansion of UCB HSCs is still to be explored
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