Diabetes limits stem cell mobilization following G-CSF but not plerixafor

Gian Paolo Fadini, Mark Fiala, Roberta Cappellari, Marianna Danna, Soo Park, Nicol Poncina, Lisa Menegazzo, Mattia Albiero, John Dipersio, Keith Stockerl-Goldstein, Angelo Avogaro

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38 Scopus citations

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-CSFwas less effective in patientswith 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.

Original languageEnglish
Pages (from-to)2969-2977
Number of pages9
JournalDiabetes
Volume64
Issue number8
DOIs
StatePublished - Aug 2015

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