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基于SCI动态病理变化的多靶向治疗促脊髓再生修复及相关机制研究
结题报告
批准号:
81830077
项目类别:
重点项目
资助金额:
297.0 万元
负责人:
郝定均
依托单位:
学科分类:
骨、关节、软组织损伤与修复
结题年份:
2023
批准年份:
2018
项目状态:
已结题
项目参与者:
郝定均
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中文摘要
脊髓损伤(SCI)后多因素动态病理变化已成为脊髓再生修复治疗和功能重建的瓶颈,目前尚无有效治疗手段。因此有效对接SCI动态病理变化的多靶向治疗对脊髓再生修复尤为重要。我们前期研究发现嗅鞘细胞(OEC)在CCM等分子持续作用下其吞噬免疫调节、增殖及分泌功能显著放大,精原干细胞(SSC)在特定条件下可被诱导分化为脊髓神经元。本项目拟以OEC和SSC为切入点,采用SAP包裹负载CCM等分子PLC生物材料缓释诱导OEC并联合SSC定向分化的综合方案,研究其对SCI动态病理变化的多靶向治疗作用。进一步通过细胞分子生物学及功能学分析等相关技术深入探讨此治疗体系对SCI动态病理变化的多靶向治疗促脊髓再生和功能重建分子机制。最终建立高效促脊髓再生多靶向精准治疗的新技术平台,为临床上诊治SCI动态病理变化提供了新的思路和手段。同时本项目将阐明多靶向治疗SCI的调控机制,为有效治疗SCI提供新的分子机制。
英文摘要
An extremely multifaceted dynamic pathological change following spinal cord injury (SCI) has been regarded as a significant bottleneck in spinal cord regeneration and function repair. Until now, there are no effective treatments. Therefore, it is pivotal solution to seek an efficient strategy to butt multitherapeutic targeting and the multifaceted pathological process to overcome the overwhelming issue, leading to remarkable improvement of SCI and function recovery. Fascinatingly, our recent studies demonstrated that olfactory ensheathing cells following a consecutively medicinal treatment such as CCM, can be activated and further maximize its cellular biofunctions including phagocytosis, immunimoduation, proliferation and secretion. Combinationally, spermatogonial stem cells (SSCs) can be converted into spinal cord neural cells under involvement of a set of defined growth factors. On the basis of the results obtained from previous project, the aims of our present project are to systematically investigate the combinatorial therapeutic roles in the multifaceted dynamic pathological change following SCI by means of neurodifferentiated SSCs and activated OECs caused by a set of bioactive molecules released from polylactic-co-caprolactone (PLC) fibrous scaffold coated by SAP. Moreover, the assessment of neural regeneration and axonal outgrowth following treatment of the combinational strategies was conducted by means of morphological, cellular and molecular, physiological animal behavior assays, and the possible mechanisms underlying the targeting strategies to treat SCI with progressive multifaceted pathology was concomitantly investigated and clarified. We will eventually develop an efficient technology platform for both multi-targeting accurate treatment of SCI and improvement of functional outcomes following lesion. Thus the present project will provide an alternative therapeutic solution for neural regeneration by the clinical application of comprehensive treatments of multifaceted SCI dynamic pathology, and elucidate the underlying mechanisms by which multitherapeutic targeting to treat SCI with progressive multifaceted pathological change results in spinal cord regeneration Meanwhile, On the other hands, it may provide novel theoretical basis for clarification of the precise molecular mechanisms in future clinical application.
期刊论文列表
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科研奖励列表
会议论文列表
专利列表
DOI:10.3389/fendo.2022.1081185
发表时间:2022
期刊:FRONTIERS IN ENDOCRINOLOGY
影响因子:5.2
作者:Jiang, Chao;Chen, Zhe;Wang, Xiaohui;Zhang, Yongyuan;Guo, Xinyu;Xu, Zhengwei;Yang, Hao;Hao, Dingjun
通讯作者:Hao, Dingjun
DOI:--
发表时间:2020
期刊:Am J Transl Res
影响因子:--
作者:Zhe Chen;Fan Hong;Zhiyuan Wang;Dingjun Hao;Hao Yang
通讯作者:Hao Yang
DOI:--
发表时间:2021
期刊:Mol Cell Biochem
影响因子:--
作者:Guoqing Yang;Yuqing He;Dingjun Hao;Hao Yang
通讯作者:Hao Yang
DOI:10.1016/j.mtbio.2023.100630
发表时间:2023-06
期刊:MATERIALS TODAY BIO
影响因子:8.2
作者:Zhang, Ying;Xu, Hailiang;Wang, Jing;Fan, Xiaochen;Tian, Fang;Wang, Zhiyuan;Lu, Botao;Wu, Weidong;Liu, Youjun;Ai, Yixiang;Wang, Xiaohui;Zhu, Lei;Jia, Shuaijun;Hao, Dingjun
通讯作者:Hao, Dingjun
DOI:10.1021/acsnano.2c12017
发表时间:2023-02
期刊:ACS nano
影响因子:17.1
作者:Weidong Wu;Shuaijun Jia;Hailiang Xu;Ziheng Gao;Zhi-yuan Wang;Botao Lu;Yixiang Ai;Youjun Liu-Youjun
通讯作者:Weidong Wu;Shuaijun Jia;Hailiang Xu;Ziheng Gao;Zhi-yuan Wang;Botao Lu;Yixiang Ai;Youjun Liu-Youjun
激活态OECs协同SSCs源性神经元促脊髓损伤修复的作用及分子机制
  • 批准号:
    81772357
  • 项目类别:
    面上项目
  • 资助金额:
    55.0万元
  • 批准年份:
    2017
  • 负责人:
    郝定均
  • 依托单位:
GDNF修饰的嗅鞘细胞联合小分子诱导大鼠SSCs转分化为功能性脊髓神经元的作用及分子调控机制
  • 批准号:
    81472098
  • 项目类别:
    面上项目
  • 资助金额:
    80.0万元
  • 批准年份:
    2014
  • 负责人:
    郝定均
  • 依托单位:
国内基金
海外基金