急性肺损伤和急性呼吸窘迫综合征病死率仍很高，缺乏有效药物治疗措施。间充质干细胞（MSC）促进肺损伤修复，但肺内归巢较低。凝血纤溶微环境是MSC迁移至损伤部位关键途径，而组织因子途径抑制剂（TFPI）在此过程中是关键调控因子。我们发现血管内皮细胞TFPI敲除后LPS诱导的急性肺损伤明显加重，输注MSC未明显改善TFPI敲除小鼠肺损伤，且CXCL12/CXCR4轴与MSC迁移和定植密切相关。鉴于TFPI可抑制CD26酶解CXCL12的活性，我们推测TFPI可能调控CD26/CXCL12/CXCR4通路促进MSC迁移和定植。本研究将探索TFPI联合MSC治疗肺损伤的疗效；采用小动物活体成像和活细胞工作站等方法从动物、细胞和分子水平明确TFPI调控MSC迁移关键机制。该研究将为在改善肺内凝血纤溶微环境基础上联合MSC提高治疗肺损伤疗效提供依据，为肺损伤治疗提供新思路。

The mortality of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is still high, and there is no available medicine. Mesenchymal stem cells (MSCs) promote lung injury repair, but homing is rare. The microenvironment of coagulation and fibrinolysis is involved in stem cell migration, and tissue factor pathway inhibitor (TFPI) is a key factor during this process. TFPI is a biological inhibitor of CD26 which cleaves CXCL12, thereby enhances the CXCL12/CXCR4 axis to promote stem cell migration and colonization. Our preliminary studies showed that TFPI knockout deteriorated lung injury after LPS instillation, but MSC did not significantly improve lung injury after TFPI depletion; and CXCL12/CXCR4 axis was closely related to MSC migration. Thus, we speculate that TFPI may promote MSC migration through CD26/CXCL12/CXCR4 signaling pathway. In this study, we will explore the efficacy of TFPI combined with MSC in lung injury, and use luciferase-based in vivo tracking system and Cell-IQ system to clarify key mechanisms of TFPI to regulate MSC migration and colonization from animal, cell and molecular levels. The current study will provide a basis for the improvement of coagulation fibrinolytic microenvironment combined with exogenous MSC, and offer new solutions to ALI/ARDS treatment.