负载外泌体FGF10的取向水凝胶调控eNSCs定向迁移及凋亡促进脊髓损伤修复机制研究

批准号:
81901255
项目类别:
青年科学基金项目
资助金额:
20.5 万元
负责人:
李小龙
依托单位:
学科分类:
H0910.神经损伤、修复与再生
结题年份:
2022
批准年份:
2019
项目状态:
已结题
项目参与者:
--
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中文摘要
脊髓损伤是脊柱外科多发病,目前尚缺乏有效治疗手段,组织工程技术为脊髓损伤修复提供了可能。课题组制备了用于修复脊髓损伤的葡聚糖-明胶水凝胶支架,可引导间充质干细胞取向性生长。作为新兴热点,外泌体为脊髓损伤的修复提供了新的方向,与细胞移植相比,无细胞疗法不存在外源性细胞分化、突变、致瘤性等风险。神经干细胞外泌体FGF10具有神经保护作用,同时可激活Akt通路,因此,本研究提出无细胞脊髓再生策略,拟构建负载外泌体FGF10的功能化取向水凝胶用于修复脊髓损伤。本项目拟在前期工作基础上:①构建取向性水凝胶支架材料,探讨其应用于脊髓损伤修复的可行性;②将NSCs-Exos-FGF10负载于水凝胶材料中,验证其修复脊髓损伤修复的可能性;③明确取向性水凝胶材料及NSCs-Exos-FGF10优化损伤脊髓微环境的效果,及诱导内源性神经干细胞定向迁移、抑制凋亡的效果及机制,为脊髓损伤修复提供新的研究方向。
英文摘要
Spinal cord injury is a frequently-occurring disease in spinal surgery. At present, there is a lack of effective treatment methods. Tissue engineering technology provides the possibility for the repair of spinal cord injury. In the early stage, the research group prepared dextran-gelatin hydrogel scaffolds for the repair of spinal cord injury, which can guide the directional growth of mesenchymal stem cells. As a new hot spot, exosomes provide a new direction for the repair of spinal cord injury. Compared with cell transplantation, cell-free therapy has no risk of exogenous cell differentiation, mutation, tumorigenicity and so on. Neural stem cell exosomes FGF10 has neuroprotective effect and can activate Akt pathway. Therefore, a cell-free spinal cord regeneration strategy was proposed in this study, and a functionalized oriented hydrogel loaded with exosomes FGF10 was constructed to repair spinal cord injury. On the basis of previous work, this project intends to: (1) construct directional hydrogel scaffolds and explore the feasibility of their application in the repair of spinal cord injury; (2) load NSCs-Exos-FGF10 into hydrogel materials, to verify the possibility of repairing spinal cord injury, (3) to clarify the effect of directional hydrogel material and NSCs-Exos-FGF10 on optimizing the microenvironment of injured spinal cord, and the effect and mechanism of inducing directional migration of endogenous neural stem cells and inhibiting apoptosis, It provides a new research direction and treatment strategy for the repair of spinal cord injury.
构建取向性水凝胶支架材料,完成相关理化性能及生物学性能检测,探讨其应用于脊髓损伤修复的可行性; 采用新型的取向水凝胶生物活性脊髓作为载体,将 NSCs-Exos 负载于水凝胶材料中,验证其修复脊髓损伤修复的可能性;在专业学术刊物上发表 SCI 收录学术论文3篇;我们成功的构建了脊髓损伤特异性水凝胶支架,并构建了稳定的SD大鼠脊髓损伤模型,仿生水凝胶的设计为我们的临床转化奠定了扎实的数据基础;同时,我们通过分子模拟机制,为miRNA模拟物和抗miRNA的临床和实验设计提供了指导,并为进一步工程AGO蛋白作为基因调控领域的新工具开辟了道路,病探究了Ca2+/CaM与死亡相关蛋白激酶1 (DAPK1)结合,调节细胞内信号通路相关机制。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Moist-Retaining, Self-Recoverable, Bioadhesive, and Transparent in Situ Forming Hydrogels To Accelerate Wound Healing
保湿、可自我恢复、生物粘附和透明原位形成水凝胶可加速伤口愈合
DOI:10.1021/acsami.9b17180
发表时间:2020-01-15
期刊:ACS APPLIED MATERIALS & INTERFACES
影响因子:9.5
作者:Li, Jun;Yu, Fan;Pan, Jian-Feng
通讯作者:Pan, Jian-Feng
Elucidation of the conformational dynamics and assembly of Argonaute-RNA complexes by distinct yet coordinated actions of the supplementary microRNA.
通过补充 microRNA 的独特但协调的作用阐明 Argonaute-RNA 复合物的构象动力学和组装
DOI:10.1016/j.csbj.2022.03.001
发表时间:2022
期刊:Computational and structural biotechnology journal
影响因子:6
作者:Zhuang H;Fan X;Ji D;Wang Y;Fan J;Li M;Ni D;Lu S;Li X;Chai Z
通讯作者:Chai Z
Mechanistic insights into the role of calcium in the allosteric regulation of the calmodulin-regulated death-associated protein kinase.
钙在钙调蛋白调节的死亡相关蛋白激酶变构调节中的作用的机制见解
DOI:10.3389/fmolb.2022.1104942
发表时间:2022
期刊:Frontiers in molecular biosciences
影响因子:5
作者:
通讯作者:
国内基金
海外基金
