Stem Cell-Derived Exosomes: A Comprehensive Review of Biomedical Applications, Challenges, and Future Directions.

Stem cell-derived exosomes (SC-Exos) represent an innovative therapeutic breakthrough that circumvents key limitations of direct stem cell transplantation, demonstrating significant therapeutic potential while offering distinct advantages including reduced ethical controversies, decreased immunogenicity responses, and minimized tumorigenicity risks. This review provides a systematic analysis of SC-Exos research, encompassing diverse aspects from fundamental biological mechanisms and isolation and characterization techniques to advanced engineering strategies and therapeutic applications. The review elucidates the biological foundations of exosomes, analyzes different SC-Exos types and their unique characteristics, and explores multiple functional optimization strategies to enhance SC-Exos performance. Comprehensive biomedical engineering applications of SC-Exos across diverse therapeutic domains are presented, covering tissue engineering, advanced drug delivery systems, and treatments for cardiovascular, neurological, oncological, immunological, inflammatory, reproductive, musculoskeletal, and dermatological diseases, as well as other emerging applications. Clinical translation status is evaluated through analysis of current trials, revealing favorable safety profiles and promising preliminary efficacy of SC-Exos across multiple therapeutic domains. Nevertheless, significant challenges remain in standardization of isolation and purification techniques, quality control measures, therapeutic heterogeneity, scalable production capabilities, and comprehensive biosafety evaluation protocols. Future research priorities include establishing unified isolation and purification standards, developing comprehensive functional evaluation systems, optimizing administration routes and dosing regimens, and conducting large-scale multicenter clinical trials. This review provides systematic guidance for advancing effective SC-Exos-based therapeutic solutions, ultimately facilitating their clinical translation and expanding applications across biomedical challenges.