Genome engineering of stem cells for kidney regeneration

用于肾脏再生的干细胞基因组工程

• 批准号: 10012479
• 负责人: Lauren Elizabeth Woodard
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10012479
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Adult; Affect; Allogenic; Animal Model; Animals; Aristolochic Acids; Autologous Stem Cell Transplantation; Biological Markers; Birth; Cell Line; Cell Therapy; Cells; Cessation of life; Chronic Kidney Failure; Clinic; Clinical; Data; Development; Diagnosis; Dialysis procedure; Doxycycline; Embryo; End stage renal failure; Engineering; Engraftment; Epithelial Cells; Ethics; Exhibits; Fetal Development; Fetus; Firefly Luciferases; Foundations; Gene-Modified; Genetic Diseases; Genetic Engineering; Genome; Genome engineering; Growth Factor; Histology; Home environment; Homing; Homologous Transplantation; Human; Immune; Injury; Injury to Kidney; Intensive Care Units; Ischemia; Kidney; Kidney Diseases; Kidney Transplantation; Legal patent; Life; Luciferases; Measures; Mesenchyme; Methods; Mitochondria; Modeling; Morbidity - disease rate; Mus; Mutation; Natural regeneration; Nephrology; Nephrons; Optical Tomography; Outcome; Patients; Phenotype; Population; Production; Property; Proximal Kidney Tubules; Publishing; Renal Replacement Therapy; Renal function; Reperfusion Injury; Reperfusion Therapy; Rhabdomyolysis; Severities; Site; Source; Techniques; Testing; Therapeutic; Time; Toxin; Transfection; United States; Urine; Veterans; adult stem cell; base; cancer therapy; cell type; cost; engineered stem cells; fetal; functional improvement; gene therapy; immunogenic; improved functioning; in vivo; induced pluripotent stem cell; injured; injury and repair; interest; kidney cell; kidney repair; mortality; mouse model; novel therapeutics; optical imaging; paracrine; pre-clinical; progenitor; regenerative; renal damage; repaired; stem cell therapy; stem cells; tomography; transcription factor

We propose to develop a regenerative gene and cell therapy treatment for acute kidney injury and/or chronic kidney disease. These studies are based on recent advances in isolation of adult stem cells from the urine. Urine-derived stem cells have several remarkable properties: they are easy to obtain, propagate for many passages, are multipotent, and home to sites of injury. We propose to genome modify urine-derived stem cells and track their homing in three mouse models of kidney injury (ischemia reperfusion, rhabdomyolysis, and aristolochic acid). Cells will be modified with transposons to express luciferase. This will permit tracking in live animals by optical imaging together with new techniques for advanced tomography. Biomarkers for kidney injury will be measured and compared. Histology and marker analysis will determine if stem cells have an effect on the mouse phenotype for each condition. Aim 1 seeks to compare outcomes for mice receiving urine-derived stem cells vs no treatment. In Aim 2, urine-derived stem cells will be reprogrammed into induced nephron progenitor cells and compared to past methods of deriving induced nephron progenitor cells. These cells are unique because they are similar to cells found in the cap mesenchyme and are capable of differentiating into all parts of the nephron. These aims will determine if allogeneic or autologous stem cell transplant therapies based on urine- derived stem cells may have the ability to reverse or delay kidney damage in mouse models of acute kidney injury or chronic kidney disease.

我们建议发展再生基因和细胞疗法治疗急性和/或慢性肾损伤