Saadh Mohamed J, Hussein Ahmed, Bayani Alireza, Dastafkan Shayan, Amiri Mahdie, Akbari Atie, Shahsavan Shaghayegh, Soleimani Samarkhazan Hamed, Shirani Asl Vida
Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan.
Department of Medical Analysis, Medical Laboratory Technique College, The Islamic University, Najaf, Iraq.
Med Oncol. 2025 May 6;42(6):199. doi: 10.1007/s12032-025-02742-0.
Mesenchymal stem cells (MSCs) are multipotent stromal cells valued for their immunomodulatory and regenerative properties, positioning them as a cornerstone of regenerative medicine. Their derived exosomes small extracellular vesicles laden with bioactive molecules such as proteins, lipids, and nucleic acids have emerged as critical mediators of MSC therapeutic effects. This review systematically explores the biology of MSC-derived exosomes, detailing their biogenesis, molecular composition, and pivotal roles in hematopoiesis, inflammation, and immune regulation. In hematological disorders, including leukemia, lymphoma, and myelodysplastic syndromes, these exosomes exhibit significant therapeutic potential by modulating the tumor microenvironment, enhancing hematopoietic recovery, and suppressing malignant cell proliferation. Notable findings include their ability to induce cell cycle arrest in leukemia cells via the p53 pathway and to reduce chemoresistance through targeted signaling mechanisms, such as the IRF2/INPP4B axis. However, clinical translation is hindered by several challenges, including the standardization of isolation techniques such as ultracentrifugation which are costly and susceptible to contamination as well as difficulties in optimizing large-scale production and ensuring long-term safety and efficacy. Despite these obstacles, MSC-derived exosomes offer a promising, cell-free therapeutic alternative that minimizes risks such as immune rejection and tumorigenicity associated with whole-cell therapies. Future research must prioritize the refinement of isolation and production protocols, the development of precise delivery strategies, and the execution of comprehensive safety evaluations to unlock their full clinical potential in treating hematological disorders and beyond. This review integrates recent advancements to provide a clearer understanding of their multifaceted contributions and highlights the critical gaps that remain.
间充质干细胞（MSCs）是多能基质细胞，因其免疫调节和再生特性而受到重视，使其成为再生医学的基石。它们衍生的外泌体——载有蛋白质、脂质和核酸等生物活性分子的小细胞外囊泡——已成为间充质干细胞治疗效果的关键介质。本综述系统地探讨了间充质干细胞衍生外泌体的生物学特性，详细阐述了它们的生物发生、分子组成以及在造血、炎症和免疫调节中的关键作用。在包括白血病、淋巴瘤和骨髓增生异常综合征在内的血液系统疾病中，这些外泌体通过调节肿瘤微环境、促进造血恢复和抑制恶性细胞增殖，展现出显著的治疗潜力。显著的发现包括它们能够通过p53途径诱导白血病细胞的细胞周期停滞，并通过靶向信号机制（如IRF2/INPP4B轴）降低化疗耐药性。然而，临床转化受到几个挑战的阻碍，包括诸如超速离心等分离技术的标准化，这些技术成本高昂且易受污染，以及在优化大规模生产和确保长期安全性和有效性方面存在困难。尽管有这些障碍，间充质干细胞衍生的外泌体提供了一种有前景的、无细胞的治疗选择，可将与全细胞疗法相关的免疫排斥和致瘤性等风险降至最低。未来的研究必须优先改进分离和生产方案，开发精确的递送策略，并进行全面的安全性评估，以释放它们在治疗血液系统疾病及其他疾病方面的全部临床潜力。本综述整合了近期的进展，以更清楚地了解它们的多方面贡献，并突出了仍然存在的关键差距。
