Bone marrow-derived mesenchymal stem cell therapy ameliorates renal diabetic changes in streptozotocin-induced type 1 diabetes mellitus in rats

Abstract

Diabetic nephropathy (DN) is a chronic condition and one of the leading causes of end-stage kidney disease in the world. Stem cell therapy is a promising treatment for diabetes complications. Our research aimed to elucidate the potential role of mesenchymal stem cells (MSCs) generated from bone marrow to ameliorate early diabetic kidney changes and investigate the underlying mechanism that mediates MSCs action. The study involved 40 female rats and 10 male rats as donors of stem cells. The rats were divided into four groups: control, streptozotocin-treated, IV MSCs-treated, and insulin-treated. We examined the histopathology of the kidney and the gene expression of kidney injury molecule (KIM-1), c-Jun N-terminal kinase (JNK), caspase 3, and mitogen-activated protein kinase (MAPK). We did an immunohistochemical study on phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), and the mammalian target of rapamycin (mTOR). The study found that diabetes causes renal degenerative changes and activation of the AKT-PI3K mTOR pathway, with increased KIM-1, JNK, caspase 3, and MAPK expression in renal tubular cells. However, MSCs therapy improved kidney function, decreased expression levels of KIM-1, JNK, caspase 3, and MAPK, and inactivated the AKT-PI3K mTOR pathway, suggesting bone marrow-derived MSCs therapy could be beneficial.