Liver Injury and Repopulation by Bone Marrow Stem Cells

骨髓干细胞的肝损伤和再生

• 批准号: 7650281
• 负责人: Eugene Scott Swenson
• 金额: $ 13.51万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7650281
• 关键词: Accounting; Acetoacetates; Address; Adult; Affect; Allogenic; Animals; Appearance; Autologous; Award; Blood; Blood Circulation; Bone Marrow; Bone Marrow Cells; Bone Marrow Stem Cell; Bone Marrow Transplantation; Cause of Death; Cell Proliferation; Cell Therapy; Cell fusion; Cells; Child; Chimera organism; Chronic; Cytokeratin 8; Cytokine Signaling; Development; Disease; Engraftment; Epithelial; Epithelial Cells; Epithelium; Event; Gastroenterology; Goals; Green Fluorescent Proteins; Hematopoietic Stem Cell Mobilization; Hematopoietic stem cells; Hepatic; Hepatocyte; Hepatology; Human; Injury; Investigation; Kinetics; Knockout Mice; Liver; Liver diseases; Malignant - descriptor; Marrow; Measures; Mediator of activation protein; Mentors; Modeling; Mus; Muscle Fibers; Natural regeneration; Normal Cell; Operative Surgical Procedures; Patients; Phenotype; Ploidies; Polyploidy; Postdoctoral Fellow; Process; Proliferating; Radiation; Recruitment Activity; Reporter; Research; Research Personnel; Role; Signal Transduction; Skeletal Muscle; Stem Cell Factor; Stem cells; System; Testing; Tissues; Toxin; Training; Transplantation; Tyrosinemias; Umbilical Cord Blood; Wild Type Mouse; Work; Y Chromosome; blastocyst; career; cholangiocyte; cytokine; design; developmental plasticity; embryonic stem cell; experience; injured; intrahepatic; irradiation; liver transplantation; mouse model; oval cell; peripheral blood; programs; protein expression; repaired; response; response to injury; stem cell differentiation; transgene expression

DESCRIPTION (provided by applicant): Chronic liver disease is the 10th leading cause of death in the USA, but liver transplantation is available to only a select few patients. Therefore, non-surgical alternatives are urgently needed. Surprisingly, adult bone marrow contains cells capable of engrafting the liver and treating disease. Detailed understanding of this phenomenon is necessary to advance the use of bone marrow stem cells for liver disease in humans. It has been hypothesized that injured liver releases cytokine signals to the bone marrow, stimulating the release of stem cells into the circulation and recruiting them to damaged liver, where they engraft and become liver cells. The studies proposed here are designed to determine which types and degrees of liver damage promote engraftment and differentiation of bone marrow cells into functional liver cells. The FAH knockout mouse is a model of a human liver disease called hereditary tyrosinemia, which affects children and requires liver transplantation. Cells from normal bone marrow can replace up to half of the diseased liver in FAH mice. The mechanism of repair involves fusion events between marrow-derived cells and diseased liver cells. This model will be compared with experimental liver injuries induced by either the dietary toxin, DDC, or focal liver irradiation. My investigations will address the role of cell-cell fusion, both during normal liver development, and in marrow cell engraftment in the liver. I have 3 years of post-doctoral research experience, and will shortly be completing my training in gastroenterology and hepatology. This application for the mentored K08 award is submitted with the goal of providing me with the further experience and training necessary to function as an independent investigator in hepatology. I will work under the sponsorship of Dr. Diane Krause, a leader in the field of bone marrow transplantation and stem cell differentiation. Her mentoring has enabled her previous fellows to pursue successful academic careers.

描述（由申请人提供）：