Protective effect of exosomes derived from bone marrow mesenchymal stem cells on rats with diabetic nephropathy and its possible mechanism

Objective: To investigate the effect of exosomes derived from bone marrow mesenchymal stem cells (BMMSC-Exos) on diabetic nephropathy (DN) rats and its possible mechanism.

Methods: Thirty rats were divided into the following three groups of 10 rats each: the NC group (normal rats), the DN group (rats with DN), and the BM group (DN rats injected with BMMSC-Exo). Blood glucose level, renal function, blood lipid level, and plasma viscosity of the rats were detected. Renal tissue morphology was observed using hematoxylin-eosin staining. Expression levels of JAK2 and STAT3 in rats' kidneys were measured by RT-PCR and western blot.

Results: The rats in the DN group had higher levels of blood glucose, blood lipids, and blood viscosity, worse renal function, and lower body weight than those in the NC group (all P<0.05). After treatment with BMMSC-Exos, rats in the BM group had markedly decreased levels of blood glucose, blood lipids, and blood viscosity, improved renal function, and higher body weight compared to those in the DN group (all P<0.05). The renal tissues in the NC group had intact structure, and no hyperplastic or hypertrophic cells were observed. In the DN group, the renal glomerulus and mesangial matrix were abnormal, and the capillary lumen and renal tubule lumen were depressed and blocked, accompanied by interstitial edema. Pathologic changes in the renal glomerulus and tubule in the BM group were less severe than those in the DN group. The DN rats had higher expression levels of JAK2 and STAT3 than normal rats, and the rats treated with BMMSC-Exos had lower levels of JAK2 and STAT3 compared to the DN rats (all P<0.05).

Conclusion: BMMSC-Exo can achieve a good therapeutic effect in DN, which may be due to its ability to lower the blood glucose level, improve renal function, and inhibit JAK2/STAT3 expression.