Journal
STEM CELL REPORTS
Volume 13, Issue 2, Pages 322-337Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2019.07.003
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Funding
- KAKENHI grants from the Japan Society for the Promotion of Science [JP16K19494, JP17H06177]
- Research Center Network for Realization of Regenerative Medicine, Japan Agency for Medical Research and Development
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
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Kidney formation is regulated by the balance between maintenance and differentiation of nephron progenitor cells (NPCs). Now that directed differentiation of NPCs from human induced pluripotent stem cells (iPSCs) can be achieved, maintenance and propagation of NPCs in vitro should be beneficial for regenerative medicine. Although WNT and FGF signals were previously shown to be essential for NPC propagation, the requirement for BMP/TGF beta signaling remains controversial. Here we reveal that activin has superior effects to BMP7 on maintenance efficiency of human iPSC-derived NPCs. Activin expanded ITGA8(+)/PDGFRA(-)/SIX2-GFP(+) NPCs by 5-fold per week at 80%-90% efficiency, and the propagated cells possessed robust capacity for nephron formation both in vitro and in vivo. The expanded cells also maintained their nephron-forming potential after freezing. Furthermore, the protocol was applicable to multiple non-GFP-tagged iPSC lines. Thus, our activin-based protocol will be applicable to a variety of research fields including disease modeling and drug screening.
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