Diabetes impairs mobilization of stem cells for the treatment of cardiovascular disease

Abstract

Experimental diabetes impairs bone marrow (BM) mobilization of stem and progenitor cells involved in cardiovascular repair. We aimed to ascertain whether the presence of diabetes negatively affects the mobilization of stem cells induced by granulocyte-colony stimulation factor (G-CSF) in therapeutic trials for cardiovascular disease (CVD). We conducted a meta-regression analysis of clinical trials published from 1997 to 2012 using G-CSF to yield BM stem cell mobilization in patients with CVD. We collected data on demographics, treatment regimen, degree of CD34+ cell mobilization, prevalence of diabetes and of other traditional risk factors. The primary aim was detection of a correlation between prevalence of DM and achieved CD34+ cell count after G-CSF treatment. We screened 227 articles, retrieved 96 for evaluation and retained 24 for the analysis of the primary end-point. There was a strong negative correlation between prevalence of diabetes and achieved CD34+ cell levels after G-CSF stimulation (r = -0.68; p<0.0001), while there was no correlation with other traditional risk factors. A multiple regression analysis showed that the correlation between diabetes and mobilization was independent. In 13 articles reporting pre- and post-G-CSF cell counts, the increase in CD34+ cells was also negatively correlated with prevalence of diabetes (r = -0.82; p<0.0001). In trials of BM stimulation with G-CSF for the treatment of CVD, the prevalence of diabetes is the major negative determinant of CD34+ cell mobilization. These data strongly support that diabetes impairs stem cell mobilization, with possible negative implications for CVD.