课题基金基金详情
诱导性多能干细胞内Alix水平对诱导性多能干细胞减轻肺损伤作用的影响
结题报告
批准号:
81970074
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
向萌
依托单位:
学科分类:
急性肺损伤和急性呼吸窘迫综合征
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
向萌
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中文摘要
急性肺损伤(ALI)病死率极高。干细胞治疗可减轻ALI。我们研究证实经血路播散的诱导性多能干细胞(iPSC),可部分分化为肺血管内皮细胞和肺上皮细胞,部分缓解百草枯诱导ALI和肺纤维化,但iPSC及其分化的细胞在移植后3个月内逐渐消失。我们假设延长iPSC在体内寿命可提高iPSC的治疗效果。预实验发现过表达iPSC的凋亡连接基因-2-相互作用蛋白X(Alix)水平促进iPSC凋亡,炎症刺激提高iPSC中Alix表达。据此我们推测Alix敲除可延长iPSC在体内的存活时间,延长治疗可持续性。本课题利用百草枯、内毒素诱导急慢性肺损伤模型,结合外周静脉移植过表达或敲除Alix的iPSC,从肺功能、肺血管屏障、肺泡壁屏障、组织损伤方面分析Alix表达水平差异性对iPS治疗急性损伤和肺纤维化的作用;明确Alix表达水平对iPSC存活和分化能力的影响。以期延长iPSC对损伤刺激的耐受,强化其抗损伤疗效
英文摘要
Acute lung injury (ALI) has an extremely high mortality. The stem cell therapy could partially ameliorate ALI. We confirmed that induced pluripotent stem cells (iPSC) disseminated by intravenous injection could homing to injured lung tissue, and then partially differentiate into pulmonary vascular endothelial cells and pulmonary epithelial cells. However, the iPSC and its differentiated cells gradually disappear within 3 months after transplantation. Accordingly, we assume that prolongation of iPSC survival may improve treatment outcomes in vivo. The results of preliminary experiment shown that over-expression Alix of iPSC promoted apoptosis in normal culture condition. The monocyte chemoattractant protein-1 (MCP-1/CCL2) enhanced the expression Alix of iPSC. Thus, we speculate that low-level of Alix will contribute to prolong iPSC life in vivo, then extension the treatment time. Therefore, we use the model of Paraquat and LPS secondary to lung injury with normal iPSC, overexpresses or knocks out Alix-iPSC intravenous transplantation, respectively. To analyzed differentiation of iPSC homing, differentiation and survival time in the lung tissue; clear the effect of differentiation Alix expression of iPSC on the treatment outcomes of acute injury and pulmonary fibrosis from the pulmonary function, pulmonary vascular barrier, alveolar wall barrier and tissue damaged. This will enhance the effectiveness of iPSC therapy provide a scientific basis.
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DOI:10.3389/fimmu.2023.1136290
发表时间:2023
期刊:Frontiers in immunology
影响因子:7.3
作者:
通讯作者:
DOI:10.1155/2020/1609638
发表时间:2020-03
期刊:Oxidative Medicine and Cellular Longevity
影响因子:--
作者:Shun Wang;Xiaoyu Tian;Yijun Li;R. Xue;Haochen Guan;Meng Lu;Huijun Xu;Zhibin Ye;Sifen chen;Meng Xiang
通讯作者:Shun Wang;Xiaoyu Tian;Yijun Li;R. Xue;Haochen Guan;Meng Lu;Huijun Xu;Zhibin Ye;Sifen chen;Meng Xiang
DOI:10.1177/1559325820969340
发表时间:2020-10
期刊:Dose-response : a publication of International Hormesis Society
影响因子:--
作者:Li Y;Wang S;Liu J;Li X;Lu M;Wang X;Ren Y;Li X;Xiang M
通讯作者:Xiang M
DOI:10.1111/ajt.15900
发表时间:2020-04-28
期刊:AMERICAN JOURNAL OF TRANSPLANTATION
影响因子:8.8
作者:Lu, Meng;Xue, Rong;Chen, Sifeng
通讯作者:Chen, Sifeng
急性肺损伤时HMGB1调控iPS和中性粒细胞竞争性组织归巢的作用及机制研究
  • 批准号:
    81470260
  • 项目类别:
    面上项目
  • 资助金额:
    70.0万元
  • 批准年份:
    2014
  • 负责人:
    向萌
  • 依托单位:
TLR4与NLRP3介导失血性休克启动肺血管内皮细胞炎症反应的机制研究
  • 批准号:
    81100047
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    22.0万元
  • 批准年份:
    2011
  • 负责人:
    向萌
  • 依托单位:
国内基金
海外基金