Liver Sinusoidal Endothelial Cell Progenitor Cells.

肝窦内皮细胞祖细胞。

基本信息

批准号：
8817275
负责人：
LAURIE D DELEVE
金额：
$ 35.86万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-01-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8817275
关键词：
Acute Aging Allogenic Atherosclerosis Attenuated Blood Circulation Bone Marrow CXCL12 gene Cell Therapy Data Endothelial Cells Engraftment Excision Fatty Liver Functional disorder Gelatinase B Goals Grant Health Hepatic Hepatocyte Hepatology Impairment Injury Intervention Investigation Laboratories Lead Literature Liver Liver Dysfunction Liver Regeneration Liver Stem Cell Liver diseases Matrix Metalloproteinases Normal tissue morphology Outcome Pathology Play Population Process Production Progenitor Cell Engraftment Protein Isoforms Rattus Recovery Regulation Reperfusion Injury Risk Role Serum Severities Signal Pathway Signal Transduction Stem cells Therapeutic Tissues Vascular Endothelial Growth Factors acute liver injury age related base chronic liver disease chylomicron remnant improved liver cell proliferation liver injury liver transplantation novel novel strategies prevent progenitor repaired response senescence stellate cell stem stem cell therapy therapeutic target tissue repair young adult

项目摘要

DESCRIPTION (provided by applicant): There are two populations of liver sinusoidal endothelial cell (LSEC) progenitor cells. The LSEC progenitor cells in the bone marrow play an important role in repair of liver injury and promoting liver regeneration, but play no role in norml turnover. The LSEC progenitor cells in the liver (resident LSEC progenitor cells) contribute much less to repair of liver injury and promoting liver regeneration, but are the progenitors for normal LSEC turnover. The overarching objective of this proposal is to elucidate mechanisms underlying dysfunction of LSEC progenitor cells and of progenitor cell repair with the goal of identifying therapeutic targets. Specific aim 1 is based on the hypothesis that regulation of recruitment of bone marrow LSEC progenitor cells (i.e. proliferation of LSEC progenitors in the bone marrow, mobilization of progenitors from bone marrow to the circulation, and engraftment in the liver) is impaired in chronic liver disease and that this impairment of a repair process increases the damage of acute liver injury and impairs liver regeneration in chronic liver disease. Studies will examine the effect of acute injury in chronic liver disease on bone marrow LSEC progenitor cell recruitment to the liver, establish predictors for the risk of inadequate progenitor cell recruitment, and determine whether acute injury is attenuated with progenitor cell therapy. The hypothesis for specific aim 2 is that acute liver injury alters the signaling pathways for bone marrow LSEC progenitor cell engraftment in the liver. Studies will examine the effect of altered signaling on bone marrow LSEC progenitor cell engraftment and on liver regeneration, elucidate the mechanisms that lead to the impairment of signaling, and will determine whether strategies to restore normal signaling ameliorate acute injury. The hypothesis for the third aim is that phenotypic changes in LSEC with aging are due to changes in resident progenitor cells. Studies will determine whether the changes in the LSEC are indeed due to changes in the progenitor cell and will examine the signaling pathways that lead to the changes in the resident progenitor cells.

描述（由申请人提供）：有两个肝脏正弦内皮细胞（LSEC）祖细胞的种群。骨髓中的LSEC祖细胞在修复肝损伤和促进肝脏再生方面起着重要作用，但在Norml周转中没有任何作用。肝脏中的LSEC祖细胞（居民LSEC祖细胞）在修复肝损伤和促进肝脏再生方面的贡献要少得多，但是正常LSEC离职率的祖细胞。该提案的总体目的是阐明LSEC祖细胞和祖细胞修复功能障碍的机制，目的是鉴定治疗靶标。具体目的1是基于以下假设：调节骨髓LSEC祖细胞的募集（即，骨髓中LSEC祖细胞的增殖，动员祖细胞从骨髓到循环的动员，以及在肝脏中植入的骨髓的增殖）会损害慢性疾病的损害，并在慢性疾病中受到损害的损害。慢性肝病。研究将检查急性损伤对慢性肝病的影响对肝脏祖细胞募集到肝脏的骨髓，建立预测因子，以预测祖细胞募集不足的风险，并确定是否因祖细胞疗法减弱急性损伤。特定目标2的假设是急性肝损伤改变了信号通路用于肝骨髓祖细胞植入肝脏。研究将检查信号改变对骨髓LSEC祖细胞植入和肝脏再生的影响，阐明导致信号损害的机制，并将确定是否恢复正常信号的策略是否可以缓解急性损伤。第三个目标的假设是 LSEC随着衰老而发生的表型变化是由于居民祖细胞的变化所致。研究将确定LSEC的变化是否确实是由于祖细胞的变化，并将检查导致居民祖细胞变化的信号传导途径。