目前国内外没有关于静脉壁干细胞溶解静脉血栓的报道。前期研究我们发现静脉血栓形成后静脉壁MMP9表达增加，其静脉壁Sca-1干细胞大量增殖并跨过静脉壁在血栓内募集，通过血管新生溶解血栓，但不清楚静脉壁Sca-1干细胞如何被动员并在血栓内募集。已证实干细胞动员剂通过纤溶酶活化MMP9，后者调控CXCR4的表达而动员骨髓干细胞。因静脉血栓形成后纤溶激活，活化的MMP9降解静脉壁基质。我们推测血栓形成后静脉壁活化的MMP9不仅动员静脉壁Sca-1干细胞，而且通过降解静脉壁基质而利于Sca-1干细胞跨过静脉壁在血栓内募集。本项目以血栓形成后的静脉壁Sca-1干细胞为研究对象，应用基因敲出、抗体封闭、受体拮抗、干细胞移植及示踪、Bioreactor等，研究MMP9介导静脉壁Sca-1干细胞在静脉血栓内募集的机制。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。

No reports were currently available about the role of vein wall derived stem cells playing in the resolution of venous thrombus. Our recent study shows that: After venous thrombosis, MMP9 highly expressed in the vein wall with thrombus, and lots of Sca-1 stem cells proliferated in vein wall with part of stem cells moved across vein wall and accumulated in venous thrombus.Sca-1 stem cells, derived from vein wall, enhanced the resolution of venous thrombus by neovascularization. However, the mechanism is unclear for the mobilization of vein wall derived Sca-1 stem cells and its accumulation into venous thrombus. It is well elucidated that the mobilization of bone marrow stem cell is mediated by active MMP9-dependent C-X-C chemokine receptor type 4 (CXCR4) expression on bone marrow stem cell. The activation of MMP9 is induced by plasmin which activated by mobilization agent of bone marrow stem cell. Venous thrombosis would activate the fibrinolytic system and the atctive MMP9 would degrade matrix of vein wall. We hypothesize that vein wall derived Sca-1 stem cells are mobilized by active MMP9 after venous thrombosis, and the degradation of matrix by active MMP9 facilitate Sca-1 stem cells moving across vein wall and accumulation into the venous thrombus. In this protocol, we will culture the vein wall derived Sca-1 stem cells with thrombus and study the mechanisms of MMP9 in directing accumulation of vein wall derived Sca-1 stem cells into venous thrombus by gene knockout,antibody blockage,receptor antagonist, stem cells transplantation in the adventitia of vein wall, stem cells tracing,Trans-well co-culture and Bioreactor. It would contribute to further illustrate the mechanism of natural resolution of venous thrombus and explore the new treatment of venous thrombus.