Evaluation of oxidative stress and cell death of renal cells conditioned in vitro to Diabetic Renal Disease after treatment with bone marrow mesenchymal stem cells transfected with the Klotho gene

Abstract

Diabetes mellitus (DM) is an epidemiological disease and a major public health problem, affecting people of all ages, sex, and ethnicity. It is estimated that the number of individuals affected by DM in the world are more than 425 million, and it is estimated that 629 million people will be diagnosed with DM in 2040. Due to hyperglycemia and other associated factors, diabetic nephropathy (DN) is one of the main complications caused by DM. It is a multifactorial, progressive disease that involves different cell types, molecules and signaling pathways. It is one of the most common causes of structural and functional abnormalities of the kidney. One of the main factors responsible for the complications of DM, including DN, is oxidative stress, which is caused by an imbalance between the production of reactive oxygen species (ROS) and the capacity for detoxification and damage repair, that is, the production of ROS exceeds the production of antioxidants. A possible strategy for the treatment of DN is cell therapy that has already had its therapeutic potential validated in preclinical models in both acute and chronic renal diseases. The use of bone marrow-derived mesenchymal stem cells (BM-MSCs) is therefore described in several animal models, including DN models. It presents high therapeutic potential and contributes to the improvement of the morphological and functional alterations. In addition, the therapeutic potential of BM-MSCs combined with renal progenitor cells is of great interest, since they can be genetically modified with plasmids. Klotho is an anti-aging protein with anti-oxidative, anti-apoptosis and anti-fibrosis properties. Therefore, this project aims to evaluate cell death and oxidative stress in an in vitro model of different kidney cells cultured in conditioned media characteristic of diabetic renal disease before and after treatment with BM-MSCs therapy transfected with the Klotho gene.