Effects of hyperglycemia on adipose-derived mesenchymal stromal cells: a study on their proangiogenic and immunomodulatory potential

Background. Hyperglycemia and poor glycemic control are two main features of diabetes mellitus. People affected by this disease are prone in developing serious secondary complications, which actually affect their life resulting in impaired life quality and even increased mortality. These are microvascular complications such as diabetic retinopathy (DR), diabetic nephropathy and diabetic neuropathy. The pathophysiological features of these complications are very similar and concern a progressive microvascular degeneration, which impairs the normal microvascular functions and vascular permeability. Hyperglycemia represents a connection point between all these secondary complications since high glucose has been identified as one of the causes mediating cell damage. Through years, clear evidences on hyperglycemia-mediated cell damage have been produced, leading to the elaboration of the “unifying hypothesis”. Here, glucose-mediated cell damage is explained as the result of a deleterious increase of oxidative stress in cells, which induces cell dysfunction and death. This mechanism has been demonstrated in several cell types from endothelial to neuronal cells, however, some aspects of hyperglycemia-mediated cell damages still need to be elucidated. The application of cell/stem cell-mediated therapies in diabetes and diabetic complications already gave some positive outcomes. In particular, mesenchymal stromal cells (MSC)-based interventions appeared to be safe and efficient. Thanks to their differentiating potential, proangiogenic features and immunomodulatory properties, pre-clinical studies of MSC application in DR gave very promising results. For instance, in animal models of DR, MSC applications often resulted in positive outcomes, delaying the progression of the disease, reducing vascular permeability and restoring functionality. However, the majority of studies used an allogenic approach proposing the application of MSC from healthy donors. Indeed, MSC from diabetic donors often revealed to be impaired by the ...