title: Diabetes Limits Stem Cell Mobilization Following G-CSF but Not Plerixafor.
abstract: Previous studies suggest that diabetes impairs hematopoietic stem cell (HSC) mobilization in response to granulocyte colony-stimulating factor (G-CSF). In this study, we tested whether the CXCR4 antagonist plerixafor, differently from G-CSF, is effective in mobilizing HSCs in patients with diabetes. In a prospective study, individuals with and without diabetes (n = 10/group) were administered plerixafor to compare CD34(+) HSC mobilization; plerixafor was equally able to mobilize CD34(+) HSCs in the two groups, whereas in historical data, G-CSF was less effective in patients with diabetes. In a retrospective autologous transplantation study conducted on 706 patients, diabetes was associated with poorer mobilization in patients who received G-CSF with/without chemotherapy, whereas it was not in patients who received G-CSF plus plerixafor. Similarly in an allogeneic transplantation study (n = 335), diabetes was associated with poorer mobilization in patients who received G-CSF. Patients with diabetes who received G-CSF without plerixafor had a lower probability of reaching >50/μL CD34(+) HSCs, independent from confounding variables. In conclusion, diabetes negatively impacted HSC mobilization after G-CSF with or without chemotherapy but had no effect on mobilization induced by G-CSF with plerixafor. This finding has major implications for the care of patients with diabetes undergoing stem cell mobilization and transplantation and for the vascular regenerative potential of bone marrow stem cells.
authors: Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy Laboratory of Experimental Diabetology, Venetian Institute of Molecular Medicine, Padova, Italy gianpaolo.fadini@unipd.it.
authors: Gian Paolo
authors: GP
authors: Fadini
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors: Mark
authors: M
authors: Fiala
authors: Laboratory of Experimental Diabetology, Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Roberta
authors: R
authors: Cappellari
authors: Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy.
authors: Marianna
authors: M
authors: Danna
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors: Soo
authors: S
authors: Park
authors: Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy Laboratory of Experimental Diabetology, Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Nicol
authors: N
authors: Poncina
authors: Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy Laboratory of Experimental Diabetology, Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Lisa
authors: L
authors: Menegazzo
authors: Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy Laboratory of Experimental Diabetology, Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Mattia
authors: M
authors: Albiero
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors: John
authors: J
authors: DiPersio
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors: Keith
authors: K
authors: Stockerl-Goldstein
authors: Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy Laboratory of Experimental Diabetology, Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Angelo
authors: A
authors: Avogaro
mesh_terms: D000328:Adult; D001596:Benzylamines; D000080027:Cyclams; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D012189:Retrospective Studies
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor