Platelet activation triggered by CD39L1/NTPDase2 facilitates CD133+/CD45* stem cell mediated liver generation

CD39L1/NTPDase2 触发的血小板激活促进 CD133 /CD45* 干细胞介导的肝脏生成

• 批准号: 144017391
• 负责人: Professor Dr. Moritz Schmelzle
• 金额: --
• 依托单位: Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/144017391?language=en
• 关键词: Platelet; activation; triggered; CD39L1; NTPDase2

Mechanisms underlying the process of homing and sequestration of CD133+ progenitor cells after liver injury and their differentiation remain unclear. Given the requirement of ectonucleotidases for vascular reconstitution during liver regeneration, we have examined within the first year whether CD133+/CD45+ BMSCs functions are dictated by purinergic ectoenzymes. We could show that CD39/NTPDase1 (and CD39L1/NTPDase2) are expressed by CD133+/CD45+ BMSCs and that purinergic signaling plays crucial roles in mobilization and function of these cells in boosting liver regeneration. Based on these observations, we plan to investigate in the second year whether and how ADP-associated platelet activation, initiated by CD39L1/NTPDase2, facilitates CD133+/CD45+ stem cell mediated liver regeneration. We will investigate liver regeneration in wild-type, CD39L1/NTPDase2 null and CD39/NTPDase1 null mice with induced thrombocytopenia or thrombocytosis following 70% hepatectomy. We plan to administer i.v. CD133+/CD45+ BMSCs from wild-type and named knock-out mice to further address the importance of local expression of ectonucleotidases.

肝损伤后CD 133+祖细胞归巢和隔离过程及其分化的机制尚不清楚。鉴于肝再生过程中血管重建需要外核苷酸酶，我们在第一年内检查了CD 133 +/CD 45 + BMSCs功能是否由嘌呤能外酶决定。我们可以证明，CD 39/NTPDase 1（和CD 39 L1/NTPDase 2）由CD 133 +/CD 45 + BMSCs表达，嘌呤能信号在这些细胞的动员和功能中起着至关重要的作用，以促进肝再生。基于这些观察，我们计划在第二年研究由CD 39 L1/NTPDase 2启动的ADP相关血小板活化是否以及如何促进CD 133 +/CD 45+干细胞介导的肝再生。我们将研究70%肝切除术后诱导血小板减少或血小板增多的野生型、CD 39 L1/NTPDase 2缺失和CD 39/NTPDase 1缺失小鼠的肝再生。我们计划通过静脉注射给予野生型和命名敲除小鼠的CD 133 +/CD 45 + BMSCs，以进一步阐明外核苷酸酶局部表达的重要性。