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集调控病灶核心区再生微环境和强化内源性修复为一体的干细胞工程化治疗系统用于脑卒中修复和再生研究

批准号:
92068110
项目类别:
重大研究计划
资助金额:
80.0 万元
负责人:
陈钧
依托单位:
学科分类:
药剂学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
陈钧

项目摘要

结项摘要

项目成果

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中文摘要
本研究针对“组织器官再生修复的有序调控与干预策略”开展研究。干细胞移植疗法因其特有的神经保护及促进神经血管修复和再生的能力,成为脑卒中治疗的新兴手段,但其疗效仍受限,集中体现在:现有策略均无法安全有效地对病灶核心区高水平活性氧和炎性因子进行调控,从而大幅提高干细胞的存活率;亦缺乏全阶段改善病灶核心区再生微环境和促进内源性再生修复的有效策略。本项目拟在前期研究基础上,结合生物纳米技术、细胞表面工程、细胞膜仿生技术和基因工程等方法,设计一种集调控卒中损伤核心区再生微环境和强化内源性修复为一体的干细胞工程化纳米屏障系统,通过静脉注射的移植方法,高度靶向损伤核心区,并高效缓冲损伤核心区高水平炎性因子和活性氧对内/外源性干细胞和周围细胞的损伤,全阶段促进内源性修复和再生。该项目为脑卒中的干细胞移植疗法提供安全、一体化的治疗新策略,也为其他组织器官再生修复提供新思路,具有较高研究价值和临床转化前景。
英文摘要
Our research will focus on the project ‘Orderly regulation and intervention strategy for tissue and organ regeneration and repair’. Stem cell transplantation therapy has become an emerging treatment of stroke due to its unique neuroprotection and ability to promote neurovascular repair and regeneration. However, its efficacy is still limited, which is mainly reflected in the following aspects: none of the existing treatment methods can safely and effectively regulate the high levels of reactive oxygen species and inflammatory factors in the core area of the lesion, so as to improve the survival rate of stem cells. And there is also a lack of effective treatment strategies to improve the regeneration microenvironment and promote endogenous regeneration and repair of stroke lesions at all stages. Based on our previous researches, this project intends to integrate bio-nanotechnology, cell surface engineering, cell membrane bio-mimic technology and genetic engineering to design a stem cell engineering ‘nano-barrier’ system with great ability to improve injury-core microenvironment and enhancing endogenous repair and regeneration. After intravenous transplantation, the engineered stem cells are expected to specifically migrate to the injury-core and effectively protect internal/external stem cells and surrounding cells from the high level inflammatory factors and reactive oxygen species in the damaged core area, and promote endogenous repair and regeneration in the whole stage. Collectively, here we propose a new safe and integrated treatment strategy for stem cell transplantation therapy for stroke, which provides new ideas for the regeneration and repair of other tissues and organs, and holds high research value and clinical transformation prospect.
期刊论文列表
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DOI: 10.1021/acsnano.3c04069
发表时间: 2023-07
期刊: ACS nano
影响因子: 17.1
作者: [Yukun Huang;Yu Chen;Songlei Zhou;Laozhi Xie;K. Liang;Jianpei Xu;Qian Zhang;Huan Chen;Dayuan Wang;Qingxiang Song;Gan Jiang;Ni Mei;Fenfen Ma;Huiping Lu;Xiaoling Gao;Jun Chen]
通讯作者: Yukun Huang;Yu Chen;Songlei Zhou;Laozhi Xie;K. Liang;Jianpei Xu;Qian Zhang;Huan Chen;Dayuan Wang;Qingxiang Song;Gan Jiang;Ni Mei;Fenfen Ma;Huiping Lu;Xiaoling Gao;Jun Chen
DOI: 10.1016/j.apsb.2023.11.009
发表时间: 2024-03-06
期刊: ACTA PHARMACEUTICA SINICA B
影响因子: 14.5
作者: [Xu,Jianpei, Sun,Yinzhe, Chen,Jun]
通讯作者: Chen,Jun
DOI: 10.1016/j.actbio.2023.09.017
发表时间: 2023-10-23
期刊: ACTA BIOMATERIALIA
影响因子: 9.7
作者: [Jiang,Tianze, Wang,Jiahao, Chen,Jun]
通讯作者: Chen,Jun
Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment.
基于二甲双胍和组蛋白脱乙酰酶抑制剂的抗炎纳米平台用于上皮间质转化抑制和转移性肿瘤治疗
DOI: 10.1186/s12951-022-01592-6
发表时间: 2022-08-31
期刊: JOURNAL OF NANOBIOTECHNOLOGY
影响因子: 10.2
作者: [Jiang, Tianze, Xie, Laozhi, Zhou, Songlei, Liu, Yipu, Huang, Yukun, Mei, Ni, Ma, Fenfen, Gong, Jingru, Gao, Xiaoling, Chen, Jun]
通讯作者: Chen, Jun
11
    病灶响应型载药系统引导神经元再生、调控再生微环境重建颅脑损伤后神经环路
    • 批准号:
      82373814
    • 项目类别:
      面上项目
    • 资助金额:
      49万元
    • 批准年份:
      2023
    • 负责人:
      陈钧
    • 依托单位:
    双重促渗机制协同提高特异性杀伤T细胞在肿瘤部位的浸润并用于免疫豁免型肿瘤的治疗
    • 批准号:
      81872498
    • 项目类别:
      面上项目
    • 资助金额:
      53.0万元
    • 批准年份:
      2018
    • 负责人:
      陈钧
    • 依托单位:
    中性粒细胞膜包覆的仿生纳米药物靶向循环肿瘤细胞与前转移病灶的治疗策略研究
    • 批准号:
      81673019
    • 项目类别:
      面上项目
    • 资助金额:
      61.0万元
    • 批准年份:
      2016
    • 负责人:
      陈钧
    • 依托单位:
    集光动力治疗、化疗于一体的卟啉-聚己内酯纳米粒的设计及其多模式肿瘤靶向治疗策略研究
    • 批准号:
      81373353
    • 项目类别:
      面上项目
    • 资助金额:
      65.0万元
    • 批准年份:
      2013
    • 负责人:
      陈钧
    • 依托单位:
    国内基金
    海外基金