Glomerular mesangial cells mitochondrial dynamics alterations in hyperglycemia followed by mesenchymal stem cell therapy

Abstract

Diabetes is an epidemic disease with increasing incidence over the world, causing multiple complications. Diabetic Nephropathy is one of the main disturbs caused by diabetic hyperglycemia, which is characterized by progressive loss of glomerular filtration rate and affects over 40% of diabetic patients. Oxidative stress, which is one of the main players in Diabetic Nephropathy pathogenesis development, affects especially, in a way that disturbs oxidative phosphorylation and culminates in even more ROS production. Increasing body of evidences demonstrates mitochondria impairment as a causal link of the main Diabetes damage pathways and also that interventions to equilibrate mitochondria dynamics can prevent alterations caused by hyperglycemia. Mitochondria have a special - however limited - ability to deal with insults, which is called Quality Control Program (biogenesis, mitophagy, fusion, fission). Cell therapy is a promising treatment tool for diabetic nephropathy, and recently it has been demonstrated that besides the well described paracrine effects, mesenchymal stem cells have the ability to directly transfer their own mitochondria to damaged cells. Our research aims to apply stem cell therapy in a diabetic nephropathy in vitro model and also to assess the influence of direct mitochondria transfer in regeneration efficacy. Finally, one of the questions to be elucidated is: what is the importance to have stem cells present and directly making contact with the injured cells? (AU)