Bavafa Amir, Izadpanahi Maryam, Hosseini Elham, Hajinejad Mehrdad, Abedi Mahsa, Forouzanfar Fatemeh, Sahab-Negah Sajad
Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 25. doi: 10.1007/s00210-024-03762-9.
Exosomes are extracellular vesicles that received attention for their potential use in the treatment of various injuries. They communicate intercellularly by transferring genetic and bioactive molecules from parent cells. Although exosomes hold immense promise for treating neurodegenerative and oncological diseases, their actual clinical use is very limited because of their biogenesis and secretion. Recent studies have shown that small molecules can significantly enhance exosome biogenesis, thereby remarkably improving yield, functionality, and therapeutic effects. These molecules modulate critical pathways toward optimum exosome production in a mode that is either ESCRT dependent or ESCRT independent. Improved exosome biogenesis may provide new avenues for targeted cancer therapy, neuroprotection in neurodegenerative diseases, and regenerative medicine in wound healing. This review explores the role of small molecules in enhancing exosome biogenesis and secretion, highlights their underlying mechanisms, and discusses emerging clinical applications. By addressing current challenges and focusing on translational opportunities, this study provides a foundation for advancing cell-free therapies in regenerative medicine and beyond.
外泌体是细胞外囊泡,因其在治疗各种损伤方面的潜在用途而受到关注。它们通过从亲代细胞转移遗传和生物活性分子进行细胞间通讯。尽管外泌体在治疗神经退行性疾病和肿瘤疾病方面具有巨大潜力,但由于其生物发生和分泌过程,其实际临床应用非常有限。最近的研究表明,小分子可以显著增强外泌体的生物发生,从而显著提高产量、功能和治疗效果。这些分子以依赖内体分选转运复合体(ESCRT)或不依赖ESCRT的方式调节关键途径,以实现最佳的外泌体产生。改善外泌体生物发生可能为靶向癌症治疗、神经退行性疾病中的神经保护以及伤口愈合中的再生医学提供新途径。本综述探讨了小分子在增强外泌体生物发生和分泌中的作用,强调了其潜在机制,并讨论了新兴的临床应用。通过应对当前挑战并关注转化机会,本研究为推进再生医学及其他领域的无细胞疗法奠定了基础。