载TGFβ-MSCs三维打印胶原/丝素支架构建促再生免疫微环境修复SCI的机制研究

Microenvironment is the key factor affecting the axonal regeneration and neurological repair after spinal cord injury (SCI). Although the immune response is the core member of the microenvironment, the role and mechanism of the immune microenvironment for the regenerative repair of SCI remain unclear. Immune mediating tissue repair driven by scaffold material is becoming an innovative regenerative strategy. From the perspective of adaptive immune microenvironment, tissue engineering scaffolds carrying immune information is adopted to build a regeneration immune microenvironment. Optimization of collagen/silk fibroin scaffolds with unique anti-inflammatory properties are selected by considering physicochemical properties and printing parameters, and the effect of different scaffolds on adaptive immune response is evaluated. Umbilical cord mesenchymal stem cells (UCMSCs), whose immunoregulatory characteristics superior to multiple potential differentiation characteristics, are used as seed cells. Mechanism of UCMSCs differentiating Th17 cells into Treg cells through the TGFβ/Smads pathway is investigated. The three-dimensional printing collagen/silk fibroin scaffold carrying TGFβ-UCMSCs is prepared. How biological information, seed cells and scaffolds synergistically regulate the immune microenvironment and the repair of SCI nerve function is investigated. This study can provide new thought for the transformation medicine of SCI through the idea of organizing the key immune cell subgroup in the tissue engineering.

微环境是影响脊髓损伤（SCI）轴突再生和神经功能修复的关键因素。尽管免疫是微环境的核心成员，但免疫微环境对SCI再生修复的作用及机制尚不清楚。由支架材料驱动免疫介导的组织修复正在成为一种创新的再生策略。本课题拟从适应性免疫微环境的角度，借助可携带免疫信息的组织工程支架，以构建促再生免疫微环境为出发点，从理化性质和打印参数优选具有独特抑炎性质的胶原/丝素支架，观察其对SCI适应性免疫反应的作用；以免疫调控特性优于多潜能分化特性的脐带间充质干细胞（UCMSCs）作为种子细胞，探讨UCMSCs基于TGFβ/Smads通路将适应性免疫亚群Th17细胞转分化为另一亚群Treg细胞的可能机制；制备TGFβ-UCMSCs三维打印胶原/丝素支架，探讨生物信息、种子细胞和支架对免疫微环境的协同调控以及对SCI神经功能的修复。本课题提出了组织工程学控制关键免疫细胞亚群的理念，可为SCI的转化医学提供新的思路。

脊髓损伤（Spinal Cord Injury，SCI）因其高死亡率和高致残率，给家庭和社会造成极大的负担。迄今为止，SCI尚缺乏有效的治疗措施，SCI后的神经功能恢复仍是临床医师和科研工作者面临的难题。轴突再生困难，是阻碍SCI神经功能恢复的关键所在。国内外学者一致认为，SCI后轴突再生困难并非由于中枢神经轴突缺乏再生能力，而是损伤微环境抑制了轴突再生。本课题以借助组织工程学构建促再生免疫微环境为出发点，从生物材料的理化性质和打印支架的参数调节多方面选取具有独特抑炎性质的胶原/丝素支架，探讨其对SCI后免疫反应尤其是适应性免疫反应的影响；采用免疫调控特性优于多潜能分化特性的UCMSCs作为种子细胞，探讨UCMSCs基于TGF/Samds在将适应性免疫T细胞亚群Th17细胞直接转分化为Treg细胞的机制；采用TGFβ-UCMSCs三维打印胶原/丝素支架，探讨生物信息、种子细胞和生物支架协同构建免疫微环境对SCI的修复作用。研究证实：通过 3D打印胶原/丝素支架），作为一种新型的人工控释系统来治疗 SCI。研究证实：载TGFβ-UCMSCs三维打印支架构建SCI后促再生免疫微环境；过表达TGF可进一步促进UCMSCs将T细胞亚群Th17细胞转分化为另一亚群Treg细胞，从而调控SCI的适应性免疫微环境；表达TGF的UCMSCs与具有抑炎特性的胶原/丝素支架共培养，探讨携带免疫信息的生物支架对SCI后免疫微环境的影响，促进神经组织再生修复。