Dental pulp stem cell-derived small extracellular vesicle in irradiation-induced senescence
Dental pulp stem cell-derived small extracellular vesicle in irradiation-induced senescence
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DOI：
10.1016/j.bbrc.2021.08.046
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发表时间：
2021-08-26
影响因子：
3.1
通讯作者：
Hibi, Hideharu
中科院分区：
文献类型：
--
作者：
Dong, Jiao;Sakai, Kiyoshi;Hibi, Hideharu
小细胞外囊泡（sEV）促进信号分子在细胞之间的转移。我们研究了人牙髓干细胞衍生的sEV（hDPSC-sEV）对照射下颌下腺小鼠模型中细胞衰老的治疗效果。将7周龄的小鼠暴露于25戈伊辐射并随机分配至对照组、磷酸盐缓冲盐水（PBS）组或hDPSC-sEV组。在18天后照射，唾液的生产进行了测量，组织学和逆转录定量PCR分析的下颌下腺。唾液流速在PBS和hDPSC-sEV组之间没有显著差异。在hDPSC-sEV组中，表达AQP 5的腺泡细胞数量和下颌下腺中的AQP 5表达水平高于其他组。此外，与未照射的小鼠相比，25戈伊刺PBS组中的小鼠显示出较高的衰老相关β-半乳糖苷酶阳性细胞数，并上调了衰老相关基因（p16（INK 4a）、p19（Arf）、p21）和衰老相关分泌表型因子（MMP 3、IL-6、派-1、NF-κ B和TGF-β）表达，所有这些在hDPSC-sEV组中均下调。PBS组的超氧化物歧化酶水平低于hDPSC-sEV组。总之，hDPSC-sEV降低了炎症细胞因子和衰老相关基因的表达，逆转了下颂细胞中的氧化应激，从而防止了辐射诱导的细胞衰老。基于这些结果，我们希望为头颈部癌症放疗后唾液腺功能障碍的创新治疗方法的发展做出贡献。(C)2021爱思唯尔公司All rights reserved.
Small extracellular vesicles (sEV) facilitate signaling molecule transfer among cells. We examined the therapeutic efficacy of human dental pulp stem cell-derived sEV (hDPSC-sEV) against cellular senescence in an irradiated-submandibular gland mouse model. Seven-week-old mice were exposed to 25 Gy radiation and randomly assigned to control, phosphate-buffered saline (PBS), or hDPSC-sEV groups. At 18 days post-irradiation, saliva production was measured; histological and reverse transcription-quantitative PCR analyses of the submandibular glands were performed. The salivary flow rate did not differ significantly between the PBS and hDPSC-sEV groups. AQP5-expressing acinar cell numbers and AQP5 expression levels in the submandibular glands were higher in the hDPSC-sEV group than in the other groups. Furthermore, compared with non-irradiated mice, mice in the 25 Gy thorn PBS group showed a high senescence-associated-beta-galactosidase-positive cell number and upregulated senescence-related gene (p16(INK4a), p19(Arf), p21) and senescence-associated secretory phenotypic factor (MMP3, IL-6, PAI-1, NF-kappa B, and TGF-beta) expression, all of which were downregulated in the hDPSC-sEV group. Superoxide dismutase levels were lower in the PBS group than in the hDPSC-sEV group. In summary, hDPSC-sEV reduced inflammatory cytokine and senescence-related gene expression and reversed oxidative stress in submandibular cells, thereby preventing irradiation-induced cellular senescence. Based on these results, we hope to contribute to the development of innovative treatment methods for salivary gland dysfunction that develops after radiotherapy for head and neck cancer. (C) 2021 Elsevier Inc. All rights reserved.