课题基金基金详情
新型Cetuximab/FTY720功能化自组装水凝胶复合神经干细胞联合移植治疗脊髓损伤及修复机制研究
结题报告
批准号:
82002301
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
齐治平
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:
2020
项目状态:
已结题
项目参与者:
齐治平
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中文摘要
脊髓损伤(SCI)后出现中心毁损囊性变与瘢痕变等是晚期病理分子事件之一,已成为难以逾越的治疗难点。可注射水凝胶具有流动性能、原位成胶填塞缺损、搭载药物/细胞等功能而备受关注。研究表明SCI后可激活内源神经干细胞(NSCs)与外源NSCs整合促进神经元再生,但存在分化效率低、转归危像等问题。又有研究表明:西妥昔单抗(Cetuximab)可作为NSCs激动剂诱导其向神经元分化和轴突再生;芬戈莫得(FTY720)具有保护NSCs、减少SCI瘢痕形成等作用;为此,本项目原创设计一种新型Cetuximab/FTY720功能化自组装水凝胶体系,并包载NSCs原位注射移植治疗SCI。观察材料的超微结构,流变及在SCI再生内环境中通过慢病毒转染、荧光技术等探讨其生物相容性、对NSCs 的存活、增殖和分化影响并研究其对SCI治疗作用机制,本项目将为该功能化自组装水凝胶系统治疗SCI提供科学证据。
英文摘要
Central lesions and glial scar after spinal cord injury (SCI) are late pathological molecular events, which is considered to be one of the most difficult regenerative problems . Injectable hydrogels have attracted much attention as a new type of hydrogel system with flow properties, in-situ gel-filling defects, and the ability to carry drugs/cells. Studies have shown that SCI can activate endogenous neural stem cells (NSCs) and transplanted exogenous NSCs to promote neuronal regeneration, but there still are some problems such as low differentiation efficiency of NSCs. Other studies have shown that cetuximab can be used as an agonist of NSCs to induce neuronal differentiation and axonal regeneration; Fingomod (FTY720) has the effect of protecting NSCs and reducing glial scar formation; Therefore, the design of this project is to manufacture a functional self-assembling hydrogel with NSCs and Cetuximab/FTY720 as the main components. Then the novel hydrogel system was implanted into the injuried site to treat SCI. The microstructure and rheology of biomaterial was evaluated, and the effect of lentivirus transfection and fluorescence technology on the survival, proliferation and differentiation of NSCs in the SCI regeneration environment was observed, and the mechanism of its effect on SCI treatment was studies. This project will provide scientific evidence for the repair of spinal cord injury by a novel composite hydrogel system.
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DOI:10.1186/s13036-023-00368-2
发表时间:2023-07-24
期刊:JOURNAL OF BIOLOGICAL ENGINEERING
影响因子:5.6
作者:Liu, Tiemei;Zhang, Qiang;Li, Hongru;Cui, Xiaoqian;Qi, Zhiping;Yang, Xiaoyu
通讯作者:Yang, Xiaoyu
DOI:10.1016/j.cej.2021.130906
发表时间:2021-06-30
期刊:CHEMICAL ENGINEERING JOURNAL
影响因子:15.1
作者:Qi, Zhiping;Zhang, Tianhui;Pan, Su
通讯作者:Pan, Su
国内基金
海外基金