Fadini Gian Paolo, Fiala Mark, Cappellari Roberta, Danna Marianna, Park Soo, Poncina Nicol, Menegazzo Lisa, Albiero Mattia, DiPersio John, Stockerl-Goldstein Keith, Avogaro Angelo
Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy Laboratory of Experimental Diabetology, Venetian Institute of Molecular Medicine, Padova, Italy
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
Diabetes. 2015 Aug;64(8):2969-77. doi: 10.2337/db15-0077. Epub 2015 Mar 24.
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.
先前的研究表明，糖尿病会损害造血干细胞（HSC）对粒细胞集落刺激因子（G-CSF）的动员反应。在本研究中，我们测试了CXCR4拮抗剂普乐沙福是否与G-CSF不同，对糖尿病患者的HSC动员有效。在一项前瞻性研究中，对患有和未患糖尿病的个体（每组n = 10）给予普乐沙福以比较CD34(+) HSC的动员情况；普乐沙福在两组中同样能够动员CD34(+) HSCs，而在历史数据中，G-CSF在糖尿病患者中的效果较差。在一项对706例患者进行的回顾性自体移植研究中，糖尿病与接受G-CSF联合或不联合化疗的患者动员效果较差有关，而在接受G-CSF加普乐沙福的患者中则不然。同样，在一项异基因移植研究（n = 335）中，糖尿病与接受G-CSF的患者动员效果较差有关。未接受普乐沙福而仅接受G-CSF的糖尿病患者达到>50/μL CD34(+) HSCs的概率较低，且不受混杂变量影响。总之，糖尿病对G-CSF联合或不联合化疗后的HSC动员有负面影响，但对G-CSF加普乐沙福诱导的动员没有影响。这一发现对接受干细胞动员和移植的糖尿病患者的护理以及骨髓干细胞的血管再生潜力具有重要意义。
