title: Endothelium-targeted human Delta-like 1 enhances the regeneration and homing of human cord blood stem and progenitor cells.
abstract: BACKGROUND
  Umbilical 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  hD1R-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.
  
  
  CONCLUSIONS
  Our results indicated that hD1R might be applied in improving hematopoietic recovery and HSC engraftment in human UCBT.
authors.affiliation: Department of Hematology, 309th Hospital, Chinese People's Liberation Army, Hei-san hu Street #17, 100091, Beijing, China. tdmtjx@163.com.
authors.forename: Deng-Mei
authors.initials: DM
authors.lastname: Tian
authors.affiliation: Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. liangym@fmmu.edu.cn.
authors.forename: Ying-Min
authors.initials: YM
authors.lastname: Liang
authors.affiliation: Department of Hematology, 309th Hospital, Chinese People's Liberation Army, Hei-san hu Street #17, 100091, Beijing, China. zhangyongqing0725@163.com.
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Zhang
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D002135:Calcium-Binding Proteins; D004727:Endothelium / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012038:Regeneration; D014019:Tissue Donors
chemical_list: D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins