Innovative diabetes mellitus treatment strategies: Mesenchymal stem cell-based therapy and its impact on pro- and anti-inflammatory cytokines modulation

Diabetes mellitus (DM) is a metabolic condition defined by chronic hyperglycemia with serious complications, including retinopathy, neuropathy, cardiopathy, and nephropathy. DM often accelerates inflammatory responses, which traditional treatments frequently fail to control. Chronic inflammation, with an imbalance between pro-inflammatory and anti-inflammatory cytokines, causes pancreatic β-cell failure and tissue damage. Mesenchymal stem cells (MSCs) are emerging as a promising therapy because of their capacity to control immune responses and stimulate tissue repair. Interleukin-1β (IL-1β), IL-17, IL-6, and tumor necrosis factor-α (TNF-α) have crucial roles in the diabetes-associated inflammatory environment. MSC therapies reduce levels of pro-inflammatory cytokines and increase levels of anti-inflammatory cytokines, such as IL-10, IL-4, IL-13, and transforming growth factor-β (TGF-β), reducing inflammation and promoting wound healing. Moreover, the dual functions in inflammation and tissue repair of key cytokines, including TGF-β, IL-6, IL-2, IL-33, and IL-8, provide both challenges and opportunities in MSC therapy. This review explores innovative MSC-based therapies for treating DM, focusing on their modulation of pro- and anti-inflammatory cytokines. MSCs may help reduce diabetic complications by restoring the cytokine balance, increasing insulin sensitivity, and protecting organs. However, the unique source of MSCs and the complex cytokine milieu in DM warrant additional research to improve treatment strategies and ensure long-term safety and efficacy. By highlighting the potential of MSCs to improve DM treatment and enhance patient outcomes, this review attempts to provide a thorough understanding of the molecular mechanisms by which MSCs regulate cytokine activity. • MSCs could be beneficial for treating DM by influencing immune responses and facilitating tissue repair. MSCs (mADSC-EVs, ADSC-Exos, BM-MSCs, hUMSCs) address DM problems • MSC therapy reduces pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, IL-17) and elevates anti-inflammatory cytokines (e.g., TGF-β, IL-10, IL-4, IL-13), promoting wound healing and inflammation reduction • MSC therapy has challenges and potential due to the dual roles of key cytokines such as TGF-β, IL-6, IL-33, and IL-8 in inflammation and tissue repair • Combination MSC therapy with additional treatments or biomaterials (gel and natural compounds) improves DM management more aggressively via regulating cytokines.