title: DFO enhances the targeting of CD34-positive cells and improves neovascularization.
abstract: Desferrioxamine (DFO), an iron chelator, mimicked hypoxia by inhibiting HIF-1α degradation and upregulated angiogenic factors. In this experiment, we elucidated the effect of DFO on CD34-positive cell migration and neovascularization. CD34-positive cells were cultured in media with DFO or an inhibitor and subjected to in vitro tubule formation and the expression of factors. Nude mice were randomly divided into five groups of 12: control, CD34, CD34-DFO, CD34-DFO-AMD (AMD3100, CXCR4 inhibitor), and CD34-DFO-LY (LY294002, the PI3K inhibitor) groups. Limb perfusion and in vivo imaging was evaluated by laser speckle imaging (LSI) and bioluminescence imaging (BLI). Capillary density was examined 14 days after surgery, and the relevant mechanism was also explored. In vitro, DFO significantly increased the tube formation and expression of angiogenic factors in CD34-positive cells, which were blocked by the PI3K inhibitor, LY294002. DFO enhanced blood flow, the function of the ischemic hindlimb, and the levels of VEGF. Further, p-eNOS and p-Akt increased in response to the ischemia. BLI showed that DFO increased the number of CD34-positive cells targeted to the ischemic sites. Immunohistofluorescence revealed that the capillary density in the ischemic hindlimb was significantly higher in the DFO treatment group compared with the other groups. However, all of these effects were diminished by LY294002. DFO treatment enhanced CD34-positive cell targeting and improved neovascularization via the PI3K/Akt signal transduction pathway in an ischemic hindlimb.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Zijing
authors.initials: Z
authors.lastname: Du
authors.forename: Tao
authors.initials: T
authors.lastname: Zan
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Huang
authors.forename: Lingling
authors.initials: L
authors.lastname: Sheng
authors.forename: Haizhou
authors.initials: H
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000378:metabolism; D002867:Chromones / Q000008:administration & dosage; D003676:Deferoxamine / Q000008:administration & dosage; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007511:Ischemia / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009025:Morpholines / Q000008:administration & dosage; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D055647:Rats, Transgenic; D015398:Signal Transduction; D033581:Stem Cell Transplantation
chemical_list: D018952:Antigens, CD34; D054377:Chemokine CXCL12; D002867:Chromones; C515256:Cxcl12 protein, mouse; D051793:Hypoxia-Inducible Factor 1; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D003676:Deferoxamine