title: Hyperbaric oxygen improves engraftment of ex-vivo expanded and gene transduced human CD34⁺ cells in a murine model of umbilical cord blood transplantation.
abstract: Delayed engraftment and graft failure represent major obstacles to successful umbilical cord blood (UCB) transplantation. Herein, we evaluated the use of hyperbaric oxygen (HBO) therapy as an intervention to improve human UCB stem/progenitor cell engraftment in an immune deficient mouse model. Six- to eight-week old NSG mice were sublethally irradiated 24 hours prior to CD34⁺ UCB cell transplant. Irradiated mice were separated into a non-HBO group (where mice remained under normoxic conditions) and the HBO group (where mice received 2 hours of HBO therapy; 100% oxygen at 2.5 atmospheres absolute). Four hours after completing HBO therapy, both groups intravenously received CD34⁺ UCB cells that were transduced with a lentivirus carrying luciferase gene and expanded for in vivo imaging. Mice were imaged and then sacrificed at one of 10 times up to 4.5 months post-transplant. HBO treated mice demonstrated significantly improved bone marrow, peripheral blood, and spleen retention and subsequent engraftment. In addition, HBO significantly improved peripheral, spleen and bone marrow engraftment of human myeloid and B-cell subsets. In vivo imaging demonstrated that HBO mice had significantly higher ventral and dorsal bioluminescence values. These studies suggest that HBO treatment of NSG mice prior to UCB CD34⁺ cell infusion significantly improves engraftment.
authors: Division of Hematology/Oncology and Blood and Marrow Transplantation Program, 2330 Shawnee Mission Parkway, University of Kansas Medical Center, Kansas City, KS 66205, USA. Electronic address: oaljitawi@kumc.edu.
authors: Omar S
authors: OS
authors: Aljitawi
authors: Yinghua
authors: Y
authors: Xiao
authors: Jeff D
authors: JD
authors: Eskew
authors: Nikhil K
authors: NK
authors: Parelkar
authors: Megan
authors: M
authors: Swink
authors: Jeff
authors: J
authors: Radel
authors: Tara L
authors: TL
authors: Lin
authors: Bruce F
authors: BF
authors: Kimler
authors: Jonathan D
authors: JD
authors: Mahnken
authors: Joseph P
authors: JP
authors: McGuirk
authors: Hal E
authors: HE
authors: Broxmeyer
authors: George
authors: G
authors: Vielhauer
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D006931:Hyperbaric Oxygenation; D007275:Injections, Intravenous; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014183:Transplantation, Heterologous; D014916:Whole-Body Irradiation
chemical_list: D018952:Antigens, CD34; D008156:Luciferases
keywords: CD34(+); Engraftment; Hyperbaric oxygen; Umbilical cord blood
references: Semin Hematol. 2010 Jan;47(1):22-36
references: 20109609
references: Bone Marrow Transplant. 2001 Jul;28(2):163-71
references: 11509934
references: Blood. 2003 Nov 15;102(10):3478-82
references: 12946998
references: Biol Blood Marrow Transplant. 2008 Aug;14(8):867-71
references: 18640569
references: Cytotherapy. 2007;9(2):111-22
references: 17453963
references: Exp Hematol. 1995 May;23(5):461-9
references: 7536685
references: JAMA. 1990 Apr 25;263(16):2216-20
references: 2181162
references: Blood. 2013 Jul 25;122(4):491-8
references: 23673863
references: Bone Marrow Transplant. 2009 Jun;43(12):935-40
references: 19139736
references: Blood. 2005 Jan 15;105(2):567-75
references: 15367439
references: Science. 2004 Aug 13;305(5686):1000-3
references: 15310902
references: Hematology Am Soc Hematol Educ Program. 2010;2010:1-6
references: 21239763
references: Blood. 2004 Mar 15;103(6):2079-87
references: 14630817
references: Blood. 2000 Oct 15;96(8):2717-22
references: 11023503
references: Nat Med. 2004 Aug;10(8):858-64
references: 15235597
references: Clin Immunol. 2008 Jun;127(3):286-97
references: 18395491
references: Exp Hematol. 2012 Jun;40(6):445-56
references: 22306295
references: Curr Opin Hematol. 2004 Mar;11(2):102-6
references: 15257026
references: N Engl J Med. 1996 Jun 20;334(25):1642-8
references: 8628361
references: Stem Cells. 2009 Aug;27(8):1932-40
references: 19544439
references: Stem Cells Dev. 2013 Apr 1;22(7):1007-15
references: 23270493
references: Blood. 2002 Nov 1;100(9):3175-82
references: 12384415
references: Blood. 2005 Sep 15;106(6):1901-10
references: 15890683
references: AIDS Res Hum Retroviruses. 2000 Nov 1;16(16):1771-6
references: 11080825
references: Blood. 2012 Feb 23;119(8):1848-55
references: 22228628
references: Lancet Oncol. 2008 Sep;9(9):831-9
references: 18693069
references: Nat Med. 2012 Dec;18(12):1786-96
references: 23160239
references: Blood. 2007 Dec 15;110(13):4543-51
references: 17671230
references: Stem Cells Dev. 2007 Jun;16(3):347-54
references: 17610364