Differentiation of Human Pluripotent Stem Cells into Kidney Cell Lineages

人多能干细胞分化为肾细胞谱系

• 批准号: 8995260
• 负责人: JAN JENSEN
• 金额: $ 40.42万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-23 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8995260
• 关键词: 3-Dimensional; Address; Adverse effects; Artificial Kidney; Arts; Cell Culture System; Cell Culture Techniques; Cell Differentiation process; Cell Lineage; Cells; Communities; Complex; Computer software; Coupled; Data; Development; Devices; Disease model; Distal; Ductal Epithelium; Embryo; End stage renal failure; Epithelial Cells; Event; Excretory function; Future; Generations; Growth; Human; Immune response; In Vitro; Ions; Kidney; Kidney Diseases; Liquid substance; Logic; Medical; Mesenchymal; Mesoderm; Metanephric Diverticulum; Methods; Modality; Modeling; Molecular; Nephrons; Neurons; Organ; Pancreas; Patients; Pattern; Phase; Pluripotent Stem Cells; Population; Procedures; Process; Property; Protocols documentation; Regenerative Medicine; Renal function; Research; Resources; Robotics; Series; Signal Pathway; Staging; Structure; Technology; Testing; Transplantation; Urine; Water; Work; base; cell type; clinical application; clinically relevant; design; diabetic; embryonic stem cell; human embryonic stem cell; in vivo; induced pluripotent stem cell; innovation; insight; kidney cell; kidney epithelial cell; nephrogenesis; novel; novel therapeutics; progenitor; public health relevance; research study; self organization; solute; three dimensional structure; tool; wasting

 DESCRIPTION (provided by applicant): The kidney is a vital organ required for waste excretion as well as water and solute reabsorption. Its functionality relies on a range of highly specialized cells that are arranged into nephrons, the functional units of the kidney. While we understand many of the properties of the different renal cell types, we lack effective methods for their differentiation from pluripotent precursors. This single-objective collaborative project is directly addressing this question focusing on establishing the basic principles for developing pure populations of terminal differentiated kidney cells. In the UH2 phase of the project we will establish optimal differentiation conditions to obtain pure renal cell subtypes derived from human embryonic stem cells. We will do this by leveraging locally available liquid handling robotic capabilities combined with deep analytics. This innovative platform was specifically designed for directed differentiation, and will be utilized for defining optimal kidney cell differentiation/maturation conditions, starting with the current state of the art differentiation protocols. In the UH3 phase we will then test the potential of these kidney cells for future use in clinical applications. In particular, we will focus on their potential for the development of artifcial kidneys. We will examine one of the key functions of kidney epithelial cells, the ability to reabsorb ions and other solute. We, we will also assess whether the differentiated cell can be used to generate nephrons in- vitro or re-populate decellularized kidneys. Together, these aims will provide very valuable information and resources for the scientific community that will aid in developing novel therapeutic advances such as artificial kidney benefitting a wide range of patients with kidney diseases.

 描述(申请人提供)：肾脏是排泄废物以及水和溶质重吸收所必需的重要器官。它的功能依赖于一系列高度专业化的细胞，这些细胞排列成肾单位，即肾脏的功能单位。虽然我们了解不同类型肾脏细胞的许多特性，但我们缺乏有效的方法将它们与多能前体细胞区分开来。这个单一目标的合作项目直接解决了这个问题，重点是建立发展终末分化的肾脏细胞纯群体的基本原则。在该项目的UH2阶段，我们将建立从人类胚胎干细胞获得纯肾细胞亚型的最佳分化条件。我们将利用当地可用的液体处理机器人能力并结合深度分析来实现这一点。这个创新的平台是专门为定向分化而设计的，将从当前最先进的分化方案开始，用于确定最佳的肾脏细胞分化/成熟条件。在UH3阶段，我们将测试这些肾脏细胞未来用于 临床应用。特别是，我们将重点关注它们在人工肾脏发展方面的潜力。我们将研究肾上皮细胞的关键功能之一，即重新吸收离子和其他溶质的能力。我们，我们还将评估分化的细胞是否可以用来在体外产生肾单位，或者重新填充脱细胞的肾脏。总而言之，这些目标将为科学界提供非常有价值的信息和资源，帮助开发新的治疗进展，如人工肾，使广泛的肾脏疾病患者受益。