Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

Abstract

Regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) might be applied for type 1 diabetes mellitus (T1DM) treatment. Thus, we proposed in vitro assessment of adipose tissue-derived MSCs (AT-MSCs) immunomodulation on autoimmune response along with beta cell protection in streptozotocin- (STZ-) induced diabetic C57BL/6 mice model. MSCs were extracted from abdominal adipose tissue of normal mice and cultured to proliferate. Diabetic mice were prepared by administration of multiple low-doses of streptozotocin. Pancreatic islets were isolated from normal mice and splenocytes prepared from normal and diabetic mice. Proliferation, cytokine production, and insulin secretion assays were performed in coculture experiments. AT-MSCs inhibited splenocytes proliferative response to specific (islet lysate) and nonspecific (PHA) triggers in a dose-dependent manner (P < 0.05). Decreased production of proinflammatory cytokines, such as IFN-γ, IL-2, and IL-17, and increased secretion of regulatory cytokines such as TGF-β, IL-4, IL-10, and IL-13 by stimulated splenocytes were also shown in response to islet lysate or PHA stimulants (P < 0.05). Finally, we demonstrated that AT-MSCs could effectively sustain viability as well as insulin secretion potential of pancreatic islets in the presence of reactive splenocytes (P < 0.05). In conclusion, it seems that MSCs may provide a new horizon for T1DM cell therapy and islet transplantation in the future.

Adipose-Derived Stem Cell-Seeded Hydrogels Increase Endogenous Progenitor Cell Recruitment and Neovascularization in Wounds

“…These results have implications for the treatment of chronic wounds as BM-MPCs not only promote neovascularization but also produce antiinflammatory cytokines that have the potential to advance chronic wounds past the chronic low-grade inflammation typically associated with poorly healing diabetic ulcers. [35][36][37] Several methods have previously been used to recruit endogenous progenitor cells, including injection of cytokines involved in stem cell homing, such as SDF or HGF, and gene therapy. 32,38 Polymeric hydrogels seeded with stem cells, however, display several advantages over these methods.…”

Human gingiva‐derived mesenchymal stem cells alleviate inflammatory bowel disease via IL‐10 signalling‐dependent modulation of immune cells

“…Mesenchymal stem cells (MSCs) are stromal cells having the potential to differentiate along mesodermal cell lineages . Many studies have demonstrated therapeutic effects of MSCs in various inflammation‐associated diseases, such as acute kidney injury, arthritis, experimental autoimmune encephalomyelitis and diabetes . MSCs are considered a promising alternative treatment for IBD due to their unique immunomodulatory properties and ability to modulate tissue inflammation .…”

Equine metabolic syndrome impairs adipose stem cells osteogenic differentiation by predominance of autophagy over selective mitophagy

“…Adipose derived mesenchymal stem cells are characterized by multi‐lineage differentiation potential and what is more the ability to regulate immune response . They exhibit the presence of specific surface markers including CD90 + , CD105 + , CD44 + and lack expression of CD45 − , elevated proliferative potential, viability, ability to self‐renew and clonogenic potential (CFU‐fs).…”

“…IL‐6 might seriously reduce ASC stemness. Besides multipotency, ASC exhibits immunomodulatory and immunosuppressive properties, which make them even more promising tool in cellular therapies , especially in the context of their potential clinical application in EMS treatment.…”