Differentiation of Human Pluripotent Stem Cells into Kidney Cell Lineages

 描述（由申请人提供）：肾脏是排泄废物以及水和溶质重吸收所需的重要器官。它的功能依赖于一系列高度特化的细胞，这些细胞排列成肾单位，肾的功能单位。虽然我们了解不同肾细胞类型的许多特性，但我们缺乏将其从多能前体分化的有效方法。这个单一目标的合作项目直接解决了这个问题，重点是建立开发终末分化肾细胞纯群体的基本原则。在项目的UH 2阶段，我们将建立最佳的分化条件，以获得来自人胚胎干细胞的纯肾细胞亚型。我们将通过利用本地可用的液体处理机器人功能与深度分析相结合来实现这一目标。该创新平台专门设计用于定向分化，并将用于定义最佳肾细胞分化/成熟条件，从当前最先进的分化方案开始。在UH 3阶段，我们将测试这些肾细胞在未来应用中的潜力。 临床应用。特别是，我们将关注它们在人工肾开发方面的潜力。我们将检查肾脏上皮细胞的关键功能之一，重吸收离子和其他溶质的能力。我们还将评估分化的细胞是否可用于在体外产生肾单位或重新填充脱细胞肾。总之，这些目标将为科学界提供非常有价值的信息和资源，这将有助于开发新的治疗进展，如人工肾，使广泛的肾脏疾病患者受益。

 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.