Directed Differentiation of Human Pluripotent Stem Cells to Podocytes under Defined Conditions

Scientific Reports
Tongcheng QianSean P Palecek

Abstract

A major cause of chronic kidney disease (CKD) is glomerular disease, which can be attributed to a spectrum of podocyte disorders. Podocytes are non-proliferative, terminally differentiated cells. Thus, the limited supply of primary podocytes impedes CKD research. Differentiation of human pluripotent stem cells (hPSCs) into podocytes has the potential to produce podocytes for disease modeling, drug screening, and cell therapies. In the podocyte differentiation process described here, hPSCs are first induced to primitive streak-like cells by activating canonical Wnt signaling. Next, these cells progress to mesoderm precursors, proliferative nephron progenitors, and eventually become mature podocytes by culturing in a serum-free medium. Podocytes generated via this protocol adopt podocyte morphology, express canonical podocyte markers, and exhibit podocyte phenotypes, including albumin uptake and TGF-β1 triggered cell death. This study provides a simple, defined strategy to generate podocytes for in vitro modeling of podocyte development and disease or for cell therapies.

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Citations

May 19, 2020·Chemical Biology & Drug Design·Ashkan Kalantary-CharvadehMasoud Darabi
Aug 25, 2020·Stem Cells International·Patrícia de Carvalho RibeiroHeloisa Cristina Caldas
Sep 18, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ping MengLili Zhou
Sep 29, 2020·Frontiers in Physiology·Larissa de AraújoMaria Oliveira-Souza
Dec 11, 2020·Stem Cell Research & Therapy·Patrícia de Carvalho RibeiroHeloisa Cristina Caldas
Jun 4, 2021·Cell Stem Cell·Jane NguyenSharon Gerecht
Jul 14, 2021·Annual Review of Biomedical Engineering·Cynthia HajalBen M Maoz
Sep 5, 2020·Chemical Reviews·Adam M JorgensenAnthony Atala
Sep 26, 2021·Scientific Reports·Mariana Charleaux de PonteMaria Oliveira-Souza

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Methods Mentioned

BETA
flow cytometry
Assay
chip
FACS
PCR

Software Mentioned

FlowJo

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