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Cell Stem Cell. 2016 Oct 6;19(4):516-529. doi: 10.1016/j.stem.2016.07.016. Epub 2016 Aug 25.

3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors.

Author information

1
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
2
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Universidad Católica San Antonio de Murcia (UCAM), Campus de los Jerónimos, N° 135 Guadalupe, 30107 Murcia, Spain.
3
Hospital Clinic, University of Barcelona, IDIBAPS, 08036 Barcelona, Spain.
4
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
5
Department of Pediatrics and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
6
Department of Molecular Life Sciences and Institute of Medical Sciences, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
7
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
8
Fundación Dr. Pedro Guillen, Investigación Biomedica de Clinica CEMTRO, Avenida Ventisquero de la Condesa, 42, 28035 Madrid, Spain.
9
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: belmonte@salk.edu.

Abstract

Transit-amplifying nephron progenitor cells (NPCs) generate all of the nephrons of the mammalian kidney during development. Their limited numbers, poor in vitro expansion, and difficult accessibility in humans have slowed basic and translational research into renal development and diseases. Here, we show that with appropriate 3D culture conditions, it is possible to support long-term expansion of primary mouse and human fetal NPCs as well as NPCs derived from human induced pluripotent stem cells (iPSCs). Expanded NPCs maintain genomic stability, molecular homogeneity, and nephrogenic potential in vitro, ex vivo, and in vivo. Cultured NPCs are amenable to gene targeting and can form nephron organoids that engraft in vivo, functionally couple to the host's circulatory system, and produce urine-like metabolites via filtration. Together, these findings provide a technological platform for studying human nephrogenesis, modeling and diagnosing renal diseases, and drug discovery.

PMID:
27570066
DOI:
10.1016/j.stem.2016.07.016
[Indexed for MEDLINE]
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