title: Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice.
abstract: Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin(-)Sca-1(+)cKit(+) (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10-12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P < 0.01, n = 8). In db/db mice, mobilization by G-CSF or AMD3100 was either increased or unaffected (P < 0.05, n = 6 to 8). Proliferation, migration, and ischemia-induced mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy.
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, USA.
authors.forename: Goutham
authors.initials: G
authors.lastname: Vasam
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, USA.
authors.forename: Shrinidh
authors.initials: S
authors.lastname: Joshi
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, USA.
authors.forename: Yagna P R
authors.initials: YP
authors.lastname: Jarajapu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D005434:Flow Cytometry; D051379:Mice; D018919:Neovascularization, Physiologic; D054411:Receptors, Leptin / Q000172:deficiency*; D013234:Stem Cells / Q000502:physiology*
chemical_list: D054411:Receptors, Leptin; C515447:leptin receptor, mouse