Mobilization of bone marrow stem/progenitor cells by AMD3100 or G‐CSF is impaired in diabetes (1142.4)

The success of autologous cell therapies for the treatment of cardiovascular disease in patients with diabetes is dependent on mobilization of bone marrow derived stem/progenitor cells (BMSPCs). We tested the efficacy of bone marrow (BM) mobilizing agents in experimental diabetes. Mice with Streptozotocin‐induced type 1 diabetes were used either at 14 (short‐term, D‐ST) or 22 (long‐term, D‐LT) weeks of diabetes with respective age‐matched controls. BM‐derived stem/progenitor cells (BMSPCs), Sca‐1 + or c‐Kit + subsets of lineage‐negative cells (LS, LK and LSK), in peripheral blood were enumerated by flow cytometry before and after administration of AMD3100 (5 mg/Kg, s.c.) or G‐CSF (125 mcg/Kg, s.c., twice a day for four days). Basal levels of LK and LSK cells in PB were decreased in both D‐ST and D‐LT compared to age‐matched controls (Ctrl, P<0.005). LS, LK and LSK were increased by AMD3100 or G‐CSF in D‐ST. In D‐ST group, mobilization of BMSPCs by AMD3100 or G‐CSF was similar to that in controls. In D‐LT group mobilization of all three subsets of BMSPCs by AMD3100 or G‐CSF was attenuated compared to the control group (P<0.005 or P<0.001, respectively). The number of SPCs in BM and the in vitro proliferation of BM‐LS cells were decreased in D‐LT (P<0.001 vs control). These results suggest that long‐term diabetes is associated with impaired mobilization of BMSPCs to clinically used mobilizers, decreased proliferative potential and reduced number of resident BMSPCs. Grant Funding Source : Supported by NIH (P30 GM103332‐01) and AACP‐NIA