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A brief review of the applications of stem and mesenchymal cell-derived exosomes for targeted therapy and cancer drug resistance:

Authors :

Laleh Etemad-Ghazani¹ Zahra Etemadi² Reza Pashaei³

1- دانشگاه آزاد اسلامی تبریز 2- دانشگاه آزاد اسلامی تبریز 3- دانشگاه آزاد علوم و پزشکی تبریز

Keywords :

Mesenchymal stem cell،Exosome،Therapy resistance،Cancer،Extracellular vesicles،Drug resistance،Targeted therapy

Abstract :

Mesenchymal stem cell (MSC)-derived exosomes, as small extracellular vesicles carrying diverse bioactive molecules, play a pivotal role in delivering anticancer drugs and repairing radiation-induced tissue damage. Due to their intrinsic ability to target tumor cells, cross physiological barriers such as the blood-brain barrier, and exhibit reduced toxicity compared to free drugs, these exosomes have emerged as promising novel drug delivery vehicles. Numerous preclinical studies have demonstrated that MSC-derived exosomes can selectively deliver chemotherapeutic agents such as doxorubicin, paclitaxel, and bioactive compounds like TRAIL and honokiol to cancer cells, thereby enhancing therapeutic efficacy while minimizing systemic toxicity. This capability is particularly valuable in combating drug-resistant cancers such as pancreatic and colorectal cancers. Beyond their antitumor applications, MSC-derived exosomes significantly contribute to accelerating the repair of radiation-induced tissue injuries. By transferring specific microRNAs and cytokines, these vesicles promote cell proliferation, inhibit apoptosis, suppress inflammation and oxidative stress, and mitigate fibrosis progression. Experimental evidence in animal models has shown that MSC-derived exosomes effectively reduce bone loss, facilitate skin repair, and attenuate radiation-induced pulmonary fibrosis. Despite their considerable clinical potential, several challenges hinder the widespread clinical translation of MSC-derived exosomes. These include the lack of standardized protocols for classification, isolation, and storage; limitations in large-scale production; and the need for improved targeting and drug-loading methods. Accordingly, ongoing research focuses on surface engineering of exosomes to enhance targeting specificity, reduce off-target effects, and improve cargo stability. Ultimately, to accelerate the clinical translation of this technology for cancer therapy and tissue regeneration, comprehensive studies including in vivo experiments, long-term safety assessments, and large-scale clinical trials are essential. The development of standardized protocols, scale-up production techniques, and precise targeting strategies remain critical steps toward realizing the full therapeutic potential of MSC-derived exosomes.