TY - JOUR
T1 - 3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors
AU - Li, Zhongwei
AU - Araoka, Toshikazu
AU - Wu, Jun
AU - Liao, Hsin Kai
AU - Li, Mo
AU - Lazo, Marta
AU - Zhou, Bing
AU - Sui, Yinghui
AU - Wu, Min Zu
AU - Tamura, Isao
AU - Xia, Yun
AU - Beyret, Ergin
AU - Matsusaka, Taiji
AU - Pastan, Ira
AU - Rodriguez Esteban, Concepcion
AU - Guillen, Isabel
AU - Guillen, Pedro
AU - Campistol, Josep M.
AU - Izpisua Belmonte, Juan Carlos
N1 - Funding Information:
We would like to thank M. Ku and M. Chang of the H.A. and Mary K. Chapman Charitable Foundations Genomic Sequencing Core for performing RNA-seq, J.O. of Human Embryonic Stem Cell Core Facility of Sanford Consortium for Regenerative Medicine for FACS, and M. Schwarz and P. Schwarz for administrative help. T.A. was supported by The Kyoto University Foundation, The Nagai Foundation Tokyo, The Kidney Foundation, Japan (grant JKFB15-4), and the UCAM. M.L and Y.X. were supported by a California Institute for Regenerative Medicine (CIRM) Training Grant fellowship. H.K. Liao was supported by Universidad Católica San Antonio de Murcia (UCAM). E.B. was supported by a Catharina Foundation fellowship. Work in the laboratory of J.C.I.B. was supported by UCAM (mouse work), Fundacion Dr. Pedro Guillen, The G. Harold and Leila Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002), and The Moxie Foundation.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/10/6
Y1 - 2016/10/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stem.2016.07.016
DO - 10.1016/j.stem.2016.07.016
M3 - Article
C2 - 27570066
AN - SCOPUS:84992410754
SN - 1934-5909
VL - 19
SP - 516
EP - 529
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 4
ER -