title: CD34(+) expansion with Delta-1 and HOXB4 promotes rapid engraftment and transfusion independence in a Macaca nemestrina cord blood transplant model.
abstract: Umbilical cord blood (CB) transplantation is a promising therapeutic approach but continues to be associated with delayed engraftment and infections. Here, we explored in our macaque CB transplant model expansion and engraftment kinetics of cells expanded with the combination of HOXB4 and Delta-1. CB cells were divided into two equal fractions; one fraction was transduced with HOXB4 yellow fluorescent protein (YFP) and expanded on control OP9 cells, and the other was transduced with HOXB4 green fluorescent protein (GFP) and expanded on Delta-expressing OP9 cells (OP9-DL1). Both fractions were transplanted into myeloablated subjects. Neutrophil and platelet recovery occurred within 7 and 19 days respectively, which was significantly earlier than in our previous study using cells expanded with HOXB4 alone, which resulted in neutrophil recovery within 12 days (P = 0.05) and platelet recovery within 37 days (P = 0.02). Furthermore, two of three animals in the current study remained fully transfusion-independent after transplantation. By day 30, reconstitution of lymphocytes was significantly greater with the HOXB4/OP9-DL1 expanded cells in all animals (P = 0.05). In conclusion, our data show that the combination of OP9-DL1 and HOXB4 can result in increased numbers of repopulating cells, thus leading to rapid engraftment and transfusion independence in macaques transplanted with autologous, expanded CB cells.
authors.affiliation: Clinical Research Division, Department of Transplantation Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Korashon L
authors.initials: KL
authors.lastname: Watts
authors.forename: Colleen
authors.initials: C
authors.lastname: Delaney
authors.forename: Veronica
authors.initials: V
authors.lastname: Nelson
authors.forename: Grant D
authors.initials: GD
authors.lastname: Trobridge
authors.forename: Brian C
authors.initials: BC
authors.lastname: Beard
authors.forename: R Keith
authors.initials: RK
authors.lastname: Humphries
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kiem
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D001803:Blood Transfusion / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008254:Macaca nemestrina / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; C064045:delta protein; D049452:Green Fluorescent Proteins