Targeted Strategies of Adipose Stem Cells for Metabolic Diseases: Mechanisms and Clinical Translation Challenges

Metabolic diseases, such as obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and atherosclerosis, represent a growing global health burden. Adipose-derived stem cells (ADSCs) have emerged as promising therapeutic agents due to their multipotency, paracrine activity, and potential for engineering targeted interventions. This review highlights recent advances in targeted ADSC strategies, focusing on their mechanisms, clinical applications, and translational challenges. Key targeted approaches include engineered exosomes for precise immunomodulation, surface-modified ADSCs for enhanced tissue homing, and biomaterial-based delivery systems for sustained and local release. Preclinical studies have demonstrated that these strategies can significantly improve glucose homeostasis, reduce hepatic steatosis, and alleviate chronic inflammation. However, clinical translation faces hurdles, including donor-dependent heterogeneity, a lack of standardized protocols, and insufficient long-term safety data. Future efforts should prioritize the development of precision-targeted ADSC therapies through genetic engineering, functionalized biomaterials, and rigorously controlled clinical trials to fully exploit their potential to treat metabolic diseases.BackgroundMetabolic diseases are prevalent worldwide, with conditions such as metabolic dysfunction-associated steatotic liver disease(MASLD), obesity, type 2 diabetes mellitus, and atherosclerosis affecting hundreds of millions of individuals. Existing therapies struggle to address the root causes of these conditions, creating an urgent clinical need. ADSCs have gained attention as a research hotspot due to their multifunctionality; however, the literature indicates that their clinical translation faces obstacles, including cellular heterogeneity, the absence of standardized protocols, and unresolved safety concerns. This review aims to review and summarize the research progress on targeted ADSC strategies for metabolic diseases, clarify their mechanisms of action, review preclinical and clinical evidence, and provide directions to overcome translational bottlenecks.