Xenogeneic transplantation of human WJ-MSCs rescues mice from acute radiation syndrome via Nrf-2-dependent regeneration of damaged tissues.,American Journal of Transplantation

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Xenogeneic transplantation of human WJ-MSCs rescues mice from acute radiation syndrome via Nrf-2-dependent regeneration of damaged tissues.
American Journal of Transplantation ( IF 8.9 ) Pub Date : 2020-02-10 , DOI: 10.1111/ajt.15819
Mayuri Bandekar _{1,

2} , Dharmendra K Maurya _{1,

3} , Deepak Sharma _{1,

3} , Rahul Checker _{1,

3} , Vikram Gota ₄ , Nigamananda Mishra ₅ , Santosh K Sandur _{1,

3}

Affiliation

There is an unmet medical need for radiation countermeasures that can be deployed for treatment of exposed individuals during ionizing radiation (IR) accidents or terrorism. Wharton's jelly mesenchymal stem cells (WJ‐MSCs) from human umbilical cord have been shown to avoid allorecognition and induce a tissue‐regenerating microenvironment, which makes them an attractive candidate for mitigating IR injury. We found that WJ‐MSCs protected mice from a lethal dose of IR even when transplanted up to 24 hours after irradiation, and a combination of WJ‐MSCs and antibiotic (tetracycline) could further expand the window of protection offered by WJ‐MSCs. This combinatorial approach mitigated IR‐induced damage to the hematopoietic and gastrointestinal system. WJ‐MSCs increased the serum concentration of the cytoprotective cytokines granulocyte colony‐stimulating factor (G‐CSF) and IL‐6 in mice. Knockdown of G‐CSF and IL‐6 in WJ‐MSCs before injection to lethally irradiated mice or transplantation of WJ‐MSCs to lethally irradiated Nrf‐2 knockout mice significantly nullified the therapeutic protective efficacy. Hence, WJ‐MSCs could be a potential cell‐based therapy for individuals accidentally exposed to radiation.

中文翻译：

人 WJ-MSC 的异种移植通过损伤组织的 Nrf-2 依赖性再生将小鼠从急性辐射综合征中拯救出来。

对于可用于在电离辐射 (IR) 事故或恐怖主义期间治疗受照射人员的辐射对抗措施，医疗需求尚未得到满足。来自人脐带的沃顿胶质间充质干细胞 (WJ-MSCs) 已被证明可以避免异体识别并诱导组织再生微环境，这使它们成为减轻 IR 损伤的有吸引力的候选者。我们发现，即使在照射后长达 24 小时移植时，WJ-MSCs 也能保护小鼠免受致死剂量的 IR，并且 WJ-MSCs 和抗生素（四环素）的组合可以进一步扩大 WJ-MSCs 提供的保护窗口。这种组合方法减轻了 IR 对造血系统和胃肠道系统的损伤。WJ-MSCs 增加了小鼠细胞保护性细胞因子粒细胞集落刺激因子 (G-CSF) 和 IL-6 的血清浓度。在注射到受致死照射的小鼠或将 WJ-MSC 移植到受致死照射的 Nrf-2 敲除小鼠之前，敲低 WJ-MSC 中的 G-CSF 和 IL-6 显着抵消了治疗保护功效。因此，对于意外暴露于辐射的个体，WJ-MSCs 可能是一种潜在的基于细胞的疗法。

更新日期：2020-02-10

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