Influence of type 2 diabetes and obesity on adipose mesenchymal stem/stromal cell immunoregulation

Type 2 diabetes (T2D), associated with obesity, represents a state of metabolic inflammation and oxidative stress leading to insulin resistance and progressive insulin deficiency. Adipose-derived stem cells (ASCs) are adult mesenchymal stem/stromal cells identified within the stromal vascular fraction of adipose tissue. These cells can regulate the immune system and possess anti-inflammatory properties. ASCs are a potential therapeutic modality for inflammatory diseases including T2D. Patient-derived (autologous) rather than allogeneic ASCs may be a relatively safer approach in clinical perspectives, to avoid occasional anti-donor immune responses. However, patient characteristics such as body mass index (BMI), inflammatory status, and disease duration and severity may limit the therapeutic utility of ASCs. The current review presents human ASC (hASC) immunoregulatory mechanisms with special emphasis on those related to T lymphocytes, hASC implications in T2D treatment, and the impact of T2D and obesity on hASC immunoregulatory potential. hASCs can modulate the proliferation, activation, and functions of diverse innate and adaptive immune cells via direct cell-to-cell contact and secretion of paracrine mediators and extracellular vesicles. Preclinical studies recommend the therapeutic potential of hASCs to improve inflammation and metabolic indices in a high-fat diet (HFD)-induced T2D disease model. Discordant data have been reported to unravel intact or detrimentally affected immunomodulatory functions of ASCs, isolated from patients with obesity and/or T2D patients, in vitro and in vivo. Numerous preconditioning strategies have been introduced to potentiate hASC immunomodulation; they are also discussed here as possible options to potentiate the immunoregulatory functions of hASCs isolated from patients with obesity and T2D.