Jingyi Zhang,1,2 Xingzhao Tian,1,2 Yi Li,3 Chunyan Fang,4 Fang Yang,1 Liang Dong,1 Yifeng Shen,1 Shiyun Pu,5 Junjun Li,5 Degui Chang,1 Lanjie Lei,6 Xujun Yu1 

1TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Orthopedics Department, Chengdu Wenjiang District People’s Hospital, Chengdu, People’s Republic of China; 4Institute of Quality Standard and Testing Technology for Agro-Products, Sichuan Academy of Agricultural Sciences, Chengdu, People’s Republic of China; 5Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu Fifth People’s Hospital, Chengdu, People’s Republic of China; 6Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, People’s Republic of China

Correspondence: Xujun Yu, TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People’s Republic of China, Tel +86 13568875492, Email yuxujun@cdutcm.edu.cn Lanjie Lei, Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, People’s Republic of China, Email leilanjie1988@163.com

Abstract: 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.

Keywords: stem cell-derived exosomes, biomedical applications, clinical translation, extracellular vesicles, biomedical engineering, nanomedicine