title: 3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors.
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.
authors: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Zhongwei
authors: Z
authors: Li
authors: 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.
authors: Toshikazu
authors: T
authors: Araoka
authors: 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.
authors: Jun
authors: J
authors: Wu
authors: 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.
authors: Hsin-Kai
authors: HK
authors: Liao
authors: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Mo
authors: M
authors: Li
authors: Hospital Clinic, University of Barcelona, IDIBAPS, 08036 Barcelona, Spain.
authors: Marta
authors: M
authors: Lazo
authors: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Bing
authors: B
authors: Zhou
authors: Department of Pediatrics and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Yinghui
authors: Y
authors: Sui
authors: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Min-Zu
authors: MZ
authors: Wu
authors: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Isao
authors: I
authors: Tamura
authors: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Yun
authors: Y
authors: Xia
authors: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Ergin
authors: E
authors: Beyret
authors: Department of Molecular Life Sciences and Institute of Medical Sciences, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
authors: Taiji
authors: T
authors: Matsusaka
authors: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Ira
authors: I
authors: Pastan
authors: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Concepcion
authors: C
authors: Rodriguez Esteban
authors: Fundación Dr. Pedro Guillen, Investigación Biomedica de Clinica CEMTRO, Avenida Ventisquero de la Condesa, 42, 28035 Madrid, Spain.
authors: Isabel
authors: I
authors: Guillen
authors: Fundación Dr. Pedro Guillen, Investigación Biomedica de Clinica CEMTRO, Avenida Ventisquero de la Condesa, 42, 28035 Madrid, Spain.
authors: Pedro
authors: P
authors: Guillen
authors: Hospital Clinic, University of Barcelona, IDIBAPS, 08036 Barcelona, Spain.
authors: Josep M
authors: JM
authors: Campistol
authors: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: belmonte@salk.edu.
authors: Juan Carlos
authors: JC
authors: Izpisua Belmonte
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000072669:Gene Editing; D006801:Humans; D007677:Kidney Function Tests; D051379:Mice; D009399:Nephrons / Q000166:cytology*; D038081:Organogenesis; D009940:Organoids / Q000166:cytology; D019899:Paracrine Communication; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors