DEBR/Rad Unit/ Biomedical Research Institute of the Armed Forces, 1 place du général Valérie André, 91223 Brétigny sur orge, France.
Health Phys. 2020 Jul;119(1):21-36. doi: 10.1097/HP.0000000000001264.
Nuclear accidents or acts of terrorism involving radioactive sources might lead to mass casualties irradiation. The hematopoietic system is one of the most critical and radiation-sensitive tissues because the limited life span of blood cells requires the continuous division of hematopoietic stem cells (HSCs) into the bone marrow. The radiation-induced hematopoietic syndrome, RI-HS, is an impairment of the hematopoiesis that will result in pancytopenia of various degrees. In fact, treatment with granulocyte-colony stimulating factor (G-CSF) is considered as a valuable adjunct to treatment controls in some irradiated patients. Nevertheless, these overexposed patients with bone marrow suppression have minimal medullary territories that do not allow complete recovery of hematopoiesis but lead to significant immunoreactivity following allogeneic hematopoietic stem cell transplantation (HSCT). The high morbidity and mortality of these overexposed patients is a reminder of the lack of effective treatment for hematopoietic syndrome. During the last 20 y, a therapeutic approach for mesenchymal stem cells (MSC) has been proposed for the management of accidentally irradiated victims. Many preclinical animal studies have shown that MSC, mainly by their secretory activity, in particular extracellular vesicles (EVs), contribute to the control of inflammation and promote regeneration of tissues by accelerating angiogenesis and re-epithelialization processes. Therefore, we investigated the potential effect of EVs on the reduction of early bone marrow ionization toxicity, early anti-apoptotic therapy, and vascular protection in the RI-HS model. The main purpose is to propose an innovative treatment of non-patient-specific RI-HS emergency treatment in order to limit allogeneic HSC.
核事故或涉及放射性源的恐怖主义行为可能导致大量人员辐照伤亡。造血系统是最关键和对辐射最敏感的组织之一，因为血细胞的有限寿命要求造血干细胞 (HSCs) 不断分裂到骨髓中。辐射诱导的造血综合征 (RI-HS) 是造血功能的损害，将导致各种程度的全血细胞减少症。事实上，粒细胞集落刺激因子 (G-CSF) 的治疗被认为是一些辐照患者治疗控制的有价值的辅助手段。然而，这些骨髓抑制的过度暴露患者骨髓区域极小，无法完全恢复造血功能，但会导致异基因造血干细胞移植 (HSCT) 后出现显著的免疫反应。这些过度暴露患者的高发病率和死亡率提醒人们，缺乏对造血综合征的有效治疗方法。在过去的 20 年中，已经提出了一种间充质干细胞 (MSC) 的治疗方法来管理意外辐照的受害者。许多临床前动物研究表明，MSC 主要通过其分泌活性，特别是细胞外囊泡 (EVs)，有助于控制炎症，并通过加速血管生成和再上皮化过程来促进组织再生。因此，我们研究了 EVs 在减少 RI-HS 模型中早期骨髓电离毒性、早期抗凋亡治疗和血管保护方面的潜在作用。主要目的是提出一种针对非患者特异性 RI-HS 的紧急治疗的创新治疗方法，以限制异基因 HSC。
