静脉壁Sca-1干细胞通过血管新生溶解静脉血栓的机制研究

Final resolution of venous thrombi depends on the natural process of organization and recanalization. Neovascularization plays an important role in the natural resolution of venous thrombi. However, it is unclear for the mechanism of neovascularization occurred in the venous thrombi. Recent evidence demonstrated that resident stem cells, found in the normal vessel wall, play a pivotal role in the development and processes of vascular disease. There were no relevant reports about stem cells in the vein wall participation in the resolution of venous thrombi. Our study shows that: ① Stem cells, derived from vein wall of vein graft, could differentiate into endothenial cells. ② After venous thrombosis, Stromal cell derived factor 1 (SDF-1) highly expressed in the thrombi, and lots of Sca-1 stem cells emerged in the vein wall and some stem cells entered into venous thrombi. Resolution of thrombi significantly increased after stem cell transplantation in the adventitia of vein wall of thrombi. It is unclear for the entering of Sca-1 stem cells into thrombi and the thrombi resolution involved by the vein wall Sca-1 stem cells.The stem cells of vein wall have clonogenic potential and promote neovascularization. Our findings showed that stem cells of vein wall, which cultured from the vein graft, could defferentiated into endothenial cells. We hypothesize that Sca-1 stem cells of vein wall are induced into venous thrombi by SDF-1, and promote neovascularization of venous thrombi and increase its resolution. In this protocol, we will culture the Sca-1 stem cells of thrombi vein wall and study the mechanisms of the cells entering into thrombi and neovascularization involving resolution of venous thrombi by cells transplantation in the adventitia of vein wall, stem cells trace, trans-well co-culture, cytokine blocking and bioreactor. It would contribute to further illustrate the natural resolution of venous thrombi and explore the new treatment of venous thrombi.

血管新生在静脉血栓自然溶解中发挥重要作用，近年发现正常静脉壁驻留有干细胞，能形成克隆并促进血管新生，但目前国内外没有关于静脉壁干细胞溶解静脉血栓的相关报道。我们前期研究发现：vein graft静脉壁干细胞能分化成内皮细胞；静脉血栓中SDF-1高表达，其静脉壁大量Sca-1干细胞，部分干细胞进入血栓，干细胞移植于血栓静脉壁外膜后血栓溶解增加。目前不清楚静脉壁干细胞如何进入血栓，进入血栓的干细胞如何溶解血栓。我们推测静脉血栓中SDF-1可能趋化静脉壁Sca-1干细胞进入血栓，进入血栓的Sca-1干细胞可能通过血管新生溶解血栓。本项目以静脉血栓形成后的静脉壁Sca-1干细胞为研究对象，应用静脉外膜干细胞移植、干细胞示踪、trans-well共培养、Bioreactor技术，研究静脉壁Sca-1干细胞通过血管新生溶解静脉血栓的机制。对进一步阐明静脉血栓自然溶解机理及探寻血栓新的疗法有重要意义。

静脉血栓是临床一严重疾病，血管新生在静脉血栓的自然溶解中发挥重要作用。目前关于血管外膜干/祖细胞在血管疾病发生、发展中的研究受到重视，但国内外没有关于静脉壁干细胞参与静脉血栓溶解的相关报道。本项目针对静脉壁干细胞溶解静脉血栓的作用进行了相关的研究，结果显示静脉壁干细胞参与静脉血栓溶解，血栓中促血管生成因子、血栓溶解相关因子的表达增加，血栓发生后静脉壁MMP9的表达显著增加，研究中也观察到进入血栓的干细胞有的表达成纤维细胞标记物。进一步研究静脉血栓形成后静脉壁干细胞动员并跨过静脉壁进入血栓内的调控因素对于探索静脉血栓新的治疗方式有重要意义。