Integrated strategies from stem cells to exosomes for amelioration of insulin resistance and promoting β-cell regeneration in diabesity.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The simultaneous epidemic of obesity and type 2 diabetes is driven by insulin resistance, chronic inflammation, and progressive β-cell dysfunction within an obese, lipotoxic microenvironment. Conventional therapies may improve glycemic control but rarely reverse the underlying metabolic damage or restore long-term homeostasis. Regenerative strategies based on stem cells such as mesenchymal stem cells (MSCs), adipose-derived stem cells (ASCs), and induced pluripotent stem cells (iPSCs), together with their extracellular vesicles (EVs) and exosomes have emerged as promising approaches to address both β-cell failure and obesity-related pathology. These interventions may restore β-cell mass and function, enhance insulin sensitivity, and remodel dysfunctional adipose tissue through direct cell replacement and paracrine signaling. This review emphasizes integrated strategies that combine stem cells, exosomes, pharmacological agents, and tissue-engineering platforms (3-D scaffolds, hydrogels, and exosome delivery systems) to achieve synergistic and more durable metabolic benefits in diabesity. Particular focus is placed on how these combinations address adipose tissue inflammation and fibrosis, ectopic lipid accumulation, brown/beige adipose tissue dysfunction, and enhance glycemic control indices. Although preclinical and early-phase clinical studies are encouraging, major challenges

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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