移植血管的免疫炎症损伤及再生的机理研究

实体器官移植是延长终末期器官疾病患者长期生存的唯一有效治疗手段，研究免疫及非免疫相关因素在器官移植的不同阶段诱导移植物损伤的作用机制是目前移植领域的研究热点。移植血管病是导致移植器官功能失调的主要原因，阐明移植排斥反应的本质及其内在机制并探索其干预策略具有重要意义。本项目基于传统的移植血管病变免疫炎症机制理论，结合多年累积的干/祖细胞参与血管重塑的预实验工作基础，提出干/祖细胞参与免疫炎症介导的移植血管损伤修复过程并扮演重要角色这一科学假说。利用谱系示踪，单细胞测序等最新研究技术及血管损伤等动物模型，探究干/祖细胞在移植血管病变不同阶段调控移植血管损伤后血管重塑的不同机制，并从来源和去路上阐述干/祖细胞参与移植免疫炎症介导的血管重塑中的重要性及其内在机制。本项目的实施有助于阐明新的导致移植血管病发生的机制，为该类疾病的防治提供新思路。

Transplantation-accelerated arteriosclerosis is one of the major challenges for long-term survival of patients with solid organ transplantation. Although stem/progenitor cells (SPCs) have been implicated to participate in this process, the cells of origin and underlying mechanisms have not been fully defined. The objective of our study was to investigate the role of SPCs in allograft-induced neointima formation, and to explore the mechanisms underlying this process. Through a combination of inducible lineage tracing and single-cell transcriptomics, we plan to perform allograft transplantation between different donor and recipient mice, bone marrow transplantation as well as parabiosis experiments, to demonstrate whether SPCs are important source of neointimal smooth muscle cells, endothelial cells and the contribution to neointima formation in an allograft transplantation model. These findings may provide novel insights into the pathogenesis of neointima formation and have further potential therapeutic implications for transplantation-related vascular diseases.