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2018 Abstracts

Nephrotic Kidney Organoids from Induced Pluripototent Stem Cells

Maxwell Beers; Jace Pulsipher, Brigham Young University

Induced pluripotent stem cells (iPSCs) are mature cells that have been reprogrammed using transcription factors to revert to pluripotent stem cells. For the past decade, researchers have been using iPSCs to generate a wide variety of different cell types in vitro. These cells have a unique advantage for potential cell therapy or organogenesis experiments, in that researchers can take cells directly from the patients, revert them to iPSCs, and then differentiate them into whatever cell type(s) are desired. This way, there is no risk of rejection in the patient, as the cells are derived from the patient’s own body. Researchers have been able to differentiate iPSCs into cells of several different organs, including heart, stomach, brain, pancreas, kidney, and more. The human kidney presents researchers with an added challenge, as mature human kidneys contain about thirty different types of cells, and even distinct varieties of progenitor cells are apparent in developing kidneys. Several different groups have, however, managed to differentiate iPSCs into small, nephrotic kidney organoids using a variety of different techniques and procedures. The main issues with the organoids produced so far are small in size and lack sufficient vascularization. The largest organoids published in current literature are only about 3-5 mm in size. Though some researchers have managed to develop organoids with potential for vascularization, they have not yet advanced past the earliest stages of development. We adapted a procedure to differentiate iPSCs into kidney organoids from one of the most successful papers to date, published by a group led by Melissa Little. We use this procedure to generate kidney organoids of our own and explore possibilities to increase the organoids’ size and vascularization, including using oxygen-carrying perfluorocarbons to increase oxygen penetration in growing cells, and implantation into severe combined immunodeficient (SCID) mice.