title: Co-transplantation with mesenchymal stem cells expressing a SDF-1/HOXB4 fusion protein markedly improves hematopoietic stem cell engraftment and hematogenesis in irradiated mice.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) contribute to the engraftment of transplanted hematopoietic stem cells (HSCs). MSCs also accelerate hematological recovery by secreting SDF-1 and enabling HSCs to enter the bone marrow (BM) via the SDF-1/CXCR4 axis. HOXB4 has been shown to stimulate HSC self-renewal. In this study, we examined whether SDF-1 and HOXB4 expression in MSCs co-transplanted with HSCs could synergistically improve hematopoietic recovery in irradiated mice.
  
  
  METHODS
  Using recombinant adenoviruses, we generated genetically modified BM-MSCs that expressed SDF-1, HOXB4, and an SDF-1/HOXB4 fusion gene. We then co-transplanted these modified MSCs with HSCs and investigated blood cell counts, BM cellularity, degree of human HSC engraftment, and survival rate in irradiated mice.
  
  
  RESULTS
  We found that co-culturing the SDF-1/HOXB4 fusion gene-modified MSCs (SDF-1/HOXB4-MSCs) and human umbilical cord blood CD34(+) cells significantly improved HSC cell expansion in vitro. More importantly, co-transplantation of CD34(+) cells and SDF-1/HOXB4-MSCs markedly increased the hematopoietic potential of irradiated mice as evidenced by the rapid recovery of WBC, PLT and HGB levels in peripheral blood and of BM cellularity. Co-transplantation also markedly improved engraftment of human CD45(+) cells in mouse BM.
  
  
  CONCLUSIONS
  Our study demonstrates that SDF-1/HOXB4-MSCs markedly accelerate hematopoietic recovery and significantly improve survival among mice treated with a lethal dose of irradiation. Therefore, SDF-1/HOXB4-MSCs could have therapeutic value by improving the efficacy of clinical transplantations in patients with defective hematopoiesis.
authors: Department of Hematology, Southwestern Hospital, Third Military Medical University Chongqing 400038, PR China.
authors: Tingting
authors: T
authors: Chen
authors: Department of Hematology, Southwestern Hospital, Third Military Medical University Chongqing 400038, PR China.
authors: Pei
authors: P
authors: Zhang
authors: Department of Hematology, Southwestern Hospital, Third Military Medical University Chongqing 400038, PR China.
authors: Wenxia
authors: W
authors: Fan
authors: Department of Hematology, Southwestern Hospital, Third Military Medical University Chongqing 400038, PR China.
authors: Fenghua
authors: F
authors: Qian
authors: Department of Hematology, Southwestern Hospital, Third Military Medical University Chongqing 400038, PR China.
authors: Li
authors: L
authors: Pei
authors: Department of Hematology, Southwestern Hospital, Third Military Medical University Chongqing 400038, PR China.
authors: Shuangnian
authors: S
authors: Xu
authors: Institute of Toxicology, Third Military Medical University Chongqing 400038, PR China.
authors: Zhongmin
authors: Z
authors: Zou
authors: Institute of Immunology PLA, Third Military Medical University Chongqing 400038, PR China.
authors: Bing
authors: B
authors: Ni
authors: Department of Hematology, Southwestern Hospital, Third Military Medical University Chongqing 400038, PR China.
authors: Yong
authors: Y
authors: Zhang
keywords: HOXB4 gene; Mesenchymal stem cells; NOD/SCID mice; SDF-1 gene; hematopoietic reconstitution; hematopoietic stem cells; irradiation
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