Treatment of Radiation Lesions with Mesenchymal Stem Cells

J. Lakota
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Abstract

   Acute radiation syndrome (ARS) is an acute illness caused by exposure to a high dose of ionizing radiation. ARS is the deterministic effect of radiation exposure of the whole body or a significant body volume (partial body irradiation) above a threshold dose of about 1 Gy (gray). Radiation accidents, such as those in Chernobyl (1986) and Fukushima (2011), or the possible use of nuclear weapons during the hostilities or terrorist attacks, can lead to the massive development of ARS in humans.   The aim of the work is to introduce a new method of post-radiation treatment – the use of allogeneic mesenchymal stem cells (MSCs).   Materials and methods. The information contained in specialized scientific journals that are freely available and accessible through the global Internet was studied.   Discussion of the results. In the scenario of mass exposure of the population, when from several tens (hundreds) to millions of people can be irradiated, the transfusion of hematopoietic stem cells traditionally used in such cases would be impossible. MSCs can possibly differentiate into specialized cells, that is, turn into cells of various organs and tissues or induce such kind of regeneration. For practical use, there are two main sources of their isolation and reproduction ex vivo – bone marrow and adipose tissue. To date, it has been shown that MSCs derived from adipose tissue can be effective in mitigating the effects of acute radiation illness. Intravenously applied MSCs are migrating mainly to the bone marrow and are partially restoring its function. Deep anatomical structures are also involved in local radiation injuries: bone, muscles, nerves, blood and lymphatic vessels and skin. There is a strong body of evidence suggesting the «repair effect» of MSCs when used to treat such lesions. This is because MSCs can induce the repair and regeneration of the anatomical structures which they are locally applied, possibly by the paracrine effect. The main advantage of allogeneic MSCs over autologous ones is their logistical accessibility. They can be produced in advance in quantities and stored frozen. After thawing, the cells must be cultured for at least 48 hours in humidified incubators with the addition of 5 % CO2.   Findings. Treatment of MSCs should be started as soon as possible after radiation exposure. Rescue of damaged hematopoiesis in the bone marrow can be achieved by multiple intravenous administration of up to 1 million (106) freshly prepared allogeneic MSCs/kg body weight. Locally (around and in the irradiation area), the dose of MSCs may be lower – 20 million cells. Repeated topical application should be carried out at intervals of two to four weeks. Subsequent surgical reconstruction should be performed by an experienced surgeon and in a specialized center with concomitant topicalapplication of MSCs.
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间充质干细胞治疗放射性病变
急性辐射综合征(ARS)是一种因暴露于高剂量电离辐射而引起的急性疾病。急性辐射反应是指超过约1戈瑞(灰色)阈值剂量的全身照射或大量身体照射(部分身体照射)所产生的确定性效应。切尔诺贝利(1986年)和福岛(2011年)等辐射事故,或在敌对行动或恐怖袭击期间可能使用核武器,都可能导致人类ARS的大规模发展。这项工作的目的是介绍一种新的放射后治疗方法-使用同种异体间充质干细胞(MSCs)。材料和方法。研究了可通过全球互联网络免费提供和获取的专门科学期刊所载的信息。结果的讨论。在人口大规模暴露的情况下,当从几十(数百)到数百万人可以受到辐射时,传统上用于这种情况的造血干细胞的输注将是不可能的。MSCs有可能分化为特化细胞,即转化为各种器官和组织的细胞或诱导这种再生。在实际应用中,它们的分离和体外繁殖有两个主要来源——骨髓和脂肪组织。迄今为止,已经证明来自脂肪组织的间充质干细胞可以有效地减轻急性辐射疾病的影响。静脉注射的间充质干细胞主要迁移到骨髓,并部分恢复其功能。局部辐射损伤还涉及深层解剖结构:骨、肌肉、神经、血液和淋巴管以及皮肤。有大量证据表明,间充质干细胞在治疗此类病变时具有“修复作用”。这是因为MSCs可以诱导局部应用的解剖结构的修复和再生,可能是通过旁分泌效应。异体间充质干细胞相对于自体间充质干细胞的主要优势在于其可获得性。它们可以提前大量生产并冷冻储存。解冻后,细胞必须在加5% CO2的加湿培养箱中培养至少48小时。发现。放射照射后应尽快开始间充质干细胞的治疗。通过多次静脉注射每公斤体重100万(106)个新鲜制备的同种异体间充质干细胞,可以挽救受损的骨髓造血功能。局部(周围和照射区域),MSCs的剂量可能较低- 2000万个细胞。应每隔两至四周重复局部应用。随后的手术重建应由经验丰富的外科医生进行,并在专业中心进行,同时局部应用间充质干细胞。
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