Effects of stem cell microenvironment on bone marrow-derived endothelial progenitor cells from diabetic mice

BACKGROUND: In patients with diabetes mellitus, the function of endothelial progenitor cells (EPCs) is impaired and the microenvironment of stem cells is disturbed. The aim of this study is to investigate whether the impairment of bone marrow EPCs from diabetic mice is caused by the disturbed stem cell microenvironment. METHODS: EPCs were isolated from bone marrow of both db/db and wild-type mice. Conditioned media was used to investigate the effects of microenvironment on EPC function in vitro. RESULTS: Diabetic EPCs produced significantly less VEGF, SDF-1a and IL-6 into their conditioned media than control cells. In consistent with this result, diabetic EPCs in their conditioned media showed significantly impaired function. After exchanging their conditioned media, the function of diabetic EPCs was partly improved, while that of control cells was impaired. Moreover, conditioned media from diabetic EPCs induced less activation of Akt and eNOS, and a higher activation of p38 MAPK compared with conditioned media from control EPCs. CONCLUSIONS: These findings suggested that the function of EPCs could be regulated by the stem cell microenvironment, and Akt/eNOS and p38 MAPK signaling pathways played an important role in the regulation of EPC function.