Efficacy of adipose‐derived mesenchymal stem cell therapy in the treatment of chronic micro‐ and macrovascular complications of diabetes

Abstract Diabetes mellitus is a highly prevalent disease characterized by hyperglycaemia that damages the vascular system, leading to micro‐ (retinopathy, neuropathy, nephropathy) and macrovascular diseases (cardiovascular disease). There are also secondary complications of diabetes (cardiomyopathy, erectile dysfunction or diabetic foot ulcers). Stem cell‐based therapies have become a promising tool targeting diabetes symptoms and its chronic complications. Among all stem cells, adipose‐derived mesenchymal stem cells (ADMSCs) are of great importance because of their abundance, non‐invasive isolation and no ethical limitations. Characteristics that make ADMSCs good candidates for cell‐based therapy are their wide immunomodulatory properties and paracrine activities through the secretion of an array of growth factors, chemokines, cytokines, angiogenic factors and anti‐apoptotic molecules. Besides, after transplantation, ADMSCs show great ex vivo expansion capacity and differentiation to other cell types, including insulin‐producing cells, cardiomyocytes, chondrocytes, hepatocyte‐like cells, neurons, endothelial cells, photoreceptor‐like cells, or astrocytes. Preclinical studies have shown that ADMSC‐based therapy effectively improved visual acuity, ameliorated polyneuropathy and foot ulceration, arrested the development and progression of diabetic kidney disease, or alleviated the diabetes‐induced cardiomyocyte hypertrophy. However, despite the positive results obtained in animal models, there are still several challenges that need to be overcome before the results of preclinical studies can be translated into clinical applications. To date, there are several clinical trials or ongoing trials using ADMSCs in the treatment of diabetic complications, most of them in the treatment of diabetic foot ulcers. This narrative review summarizes the most recent outcomes on the usage of ADMSCs in the treatment of long‐term complications of diabetes in both animal models and clinical trials.