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.

Public Health Relevance

The kidney is a multifaceted organ consisting of multiple cell types that have to work together to generate urine and retain biologically important substances such as water and ions. While many aspects of these processes are well understood, we are so far - due to the complexity of the processes taking place in vivo - unable to mimic the functions of the kidney using artificial devices. Thus, it is generally believed that any approach to replace kidney function will have to integrate in some way kidney cells. To avoid host immune responses and rejection, the cells should be ideally derived from the patient him/herself. However, conditions to generate the right cell types in sufficient amounts and purity are currently unavailable. In this proposal we will address this critical need. We will use state-of-th-art technology using a robotic- operated cell culture system coupled to a sophisticated software interface to identify conditions that allow the in vitro generation of multiple kidney cell types. e will then characterize those cells for their ability to perform some of the critical functions performed by the healthy kidney and even assemble them into kidney-like structures. Upon successful completion, the project will provide novel insights to resolve this important medical need for patients suffering from debilitating kidney diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Exploratory/Developmental Cooperative Agreement Phase II (UH3)
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Special Emphasis Panel (ZDK1)
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Hoshizaki, Deborah K
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Cleveland Clinic Lerner
Other Basic Sciences
Schools of Medicine
United States
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