Miura Yasuo, Fujii Sumie, Ichinohe Tatsuo
Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Department of Transfusion Medicine and Cell Therapy, Fujita Health University School of Medicine, 1-93 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192, Japan.
J Radiat Res. 2024 Dec 16;65(Supplement_1):i80-i87. doi: 10.1093/jrr/rrae009.
Exposure to ionizing radiation can induce harmful biological effects on the human body, particularly in cases of high-dose γ-irradiation affecting the gastrointestinal tract, bone marrow, skin and lung. Such exposures lead to lethal outcomes as individuals experience a breakdown in their immune system's ability to defend against pathogens, predisposing them to sepsis-induced multiple organ failures. Mesenchymal stromal/stem cells (MSCs) possess diverse biological characteristics, including immunomodulation, anti-inflammation and tissue regeneration. Off-the-shelf culture-expanded human bone marrow- or adipose tissue-derived MSCs are clinically available to treat graft-versus-host disease following hematopoietic cell transplantation and perianal fistulas in Crohn's disease in Japan. While preclinical studies showcase encouraging outcomes in radiation-induced injuries, the effectiveness of MSC transplantation in addressing acute radiation syndrome affecting organs in irradiated individuals is limited. Recent studies have highlighted MSC-releasing extracellular vesicles as nanoparticle substances responsible for outlining the mechanism of action and have identified various components, including proteins and microRNA, that serve as functional molecules. MSC-releasing extracellular vesicle-based therapy emerges as a promising avenue, offering a potential solution to the challenges posed by radiation-induced injuries. However, further investigation is required, especially regarding whether MSC-releasing extracellular vesicles have regenerative effects on tissue-resident stem cells. These unresolved issues represent key aspects that need to be addressed to optimize the therapeutic potential of cell-based and extracellular vesicle-based MSC therapies for interventions in the context of radiation-induced injuries.
暴露于电离辐射可对人体产生有害的生物学效应，尤其是在高剂量γ射线照射影响胃肠道、骨髓、皮肤和肺部的情况下。此类暴露会导致致命后果，因为个体的免疫系统抵御病原体的能力会崩溃，使他们易患败血症引发的多器官功能衰竭。间充质基质/干细胞（MSCs）具有多种生物学特性，包括免疫调节、抗炎和组织再生。在日本，现成的经培养扩增的人骨髓或脂肪组织来源的间充质干细胞可用于治疗造血细胞移植后的移植物抗宿主病和克罗恩病的肛周瘘管。虽然临床前研究在辐射诱导损伤方面显示出令人鼓舞的结果，但间充质干细胞移植在解决受辐射个体器官急性辐射综合征方面的有效性有限。最近的研究强调了间充质干细胞释放的细胞外囊泡作为负责阐明作用机制的纳米颗粒物质，并确定了包括蛋白质和微小RNA在内的各种成分作为功能分子。基于间充质干细胞释放的细胞外囊泡的疗法成为一条有前景的途径，为辐射诱导损伤带来的挑战提供了潜在的解决方案。然而，还需要进一步研究，特别是关于间充质干细胞释放的细胞外囊泡是否对组织驻留干细胞具有再生作用。这些未解决的问题是优化基于细胞和基于细胞外囊泡的间充质干细胞疗法在辐射诱导损伤干预中的治疗潜力时需要解决的关键方面。
