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A New Molecular Mechanism to Bioengineering a Liver

肝脏生物工程的新分子机制

基本信息

批准号：
10359794
负责人：
ERIC LAGASSE
金额：
$ 40.85万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10359794
关键词：
Address Animal Experiments Animal Model Animals BLR1 gene Biomedical Engineering CCL19 gene CXCL13 gene Cell Transplantation Cells Development Endothelial Cells Engineering Engraftment Event Failure Fatty acid glycerol esters Generations Goals Greater sac of peritoneum Growth Growth and Development function Hepatic Hepatic Mass Hepatocyte Hepatocyte transplantation Homing In Vitro Inherited Learning Liver Liver Regeneration Liver diseases Lymphatic Lymphatic System Lymphocyte Lymphoid Lymphoid Tissue Metabolic Metabolic Diseases Modeling Molecular Natural regeneration Neoplasm Metastasis Organ Organogenesis Organoids Pathway interactions Patients Peritoneal Phosphotransferases Play Population Process Property Regenerative Medicine Role Route Signal Pathway Signal Transduction Site Spottings Stromal Cells System T-Lymphocyte Tissue Engineering Translating Transplant-Related Disorder Transplantation Tumor stage base chemokine chemokine receptor clinical application clinical phenotype design drug development hepatocyte engraftment human disease in vivo insight interest liver development liver transplantation loss of function lymph nodes lymphatic Invasion lymphoid organ lymphotoxin beta receptor member neoplastic cell new therapeutic target novel receptor-mediated signaling regeneration potential regenerative scaffold secondary lymphoid organ success

项目摘要

Hepatocyte transplantation has many potential applications. Extensive animal experiments have shown that hepatocytes transplanted in the liver or at ectopic sites survive, function, and actively participate in the regenerative process. However our understanding of hepatocyte engraftment and their remarkable proliferative and regenerative potential is limited, even if primary hepatocyte transplantation is at the doorstep of applications in the treatment of inherited and acquired human diseases. We previously made a serendipitous observation that normal hepatocytes transplanted in the peritoneal cavity of an animal with lethal liver disease migrate into the lymphatic system and engineer ectopic liver-like organoids that rescue an animal model from a fatal metabolic disorder. How hepatocytes enter the lymphatics and what molecular mechanism is responsible for the generation of ectopic mass is not known. We hypothesized that hepatocytes must borrow some of the molecular mechanism lymphocytes use to migrate into the lymphatics. Our interest will be to study ectopic cell transplantation and our central objective of our application is to translate a highly interesting observation, the generation of ectopic liver, to a potential clinical application for patients with liver diseases.

肝细胞移植有许多潜在的应用。广泛的动物实验表明移植到肝脏或异位部位的肝细胞生存，功能，并积极参与再生过程。然而我们的了解肝细胞植入及其显著的增殖和再生潜力是有限的，即使原代肝细胞移植是在在治疗遗传性和获得性人类疾病的应用的门槛。我们先前偶然观察到，正常肝细胞移植到患有致死性肝病的动物的腹膜腔迁移到淋巴系统并设计异位肝样类器官，将动物模型从致命的代谢紊乱肝细胞如何进入肝细胞，导致异位肿块产生的机制尚不清楚。我们假设肝细胞必须借用一些分子机制，淋巴细胞用于迁移到淋巴细胞中。我们的兴趣将是研究异位细胞移植和我们的应用程序的中心目标是翻译一个高度有趣的观察，异位肝脏的产生，以潜在的临床应用对于肝病患者。