title: Increased Engraftment of Human Short Term Repopulating Hematopoietic Cells in NOD/SCID/IL2rγnull Mice by Lentiviral Expression of NUP98-HOXA10HD.
abstract: Techniques to expand human hematopoietic stem cells ex-vivo could be beneficial to the fields of clinical hematopoietic stem cell transplantation and gene therapy targeted at hematopoietic stem cells. NUP98-HOXA10HD is a relatively newly discovered fusion gene that in mouse transplant experiments has been shown to increase numbers of hematopoietic stem cells. We evaluated whether this fusion gene could be used to expand engrafting human primitive CD34+ cells in an immunodeficient mouse model. Gene transfer was achieved using a lentiviral based vector. The engraftment of mobilized peripheral blood human CD34+ cells grown in culture for one week after gene transfer was evaluated 3-4 months after transplant and found to be 2-3 fold higher in the NUP98-HOXA10HD groups as compared to controls. These data suggest an expansive effect at least at the short term human repopulating cell level. Further evaluation in long term repopulating models and investment in a NUP98-HOXA10HD protein seems worthy of consideration. Additionally, the results here provide strong impetus to utilize NUP98-HOXA10HD as a tool to search for underlying genes and pathways involved in hematopoietic stem cell expansion that can be enhanced and have an even more potent expansive effect.
authors.affiliation: Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
authors.forename: Allistair
authors.initials: A
authors.lastname: Abraham
authors.affiliation: Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
authors.forename: Yoon-Sang
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
authors.forename: Huifen
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 1L3, Canada.
authors.forename: Keith
authors.initials: K
authors.lastname: Humphries
authors.affiliation: Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Persons
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D015870:Gene Expression; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D023421:Models, Animal; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014161:Transduction, Genetic
chemical_list: D000954:Antigens, Surface; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D053631:Interleukin Receptor Common gamma Subunit; D028861:Nuclear Pore Complex Proteins; D011993:Recombinant Fusion Proteins; C093350:nuclear pore complex protein 98; C069634:HOXA10 protein, human