Differentiation of Human Pluripotent Stem Cells into Kidney Cell Lineages

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 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.