Journal
STEM CELL REPORTS
Volume 9, Issue 2, Pages 490-498Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.06.010
Keywords
-
Categories
Funding
- JSPS KAKENHI [16J05987, 16K18975]
- Japan Agency for Medical Research and Development [15gm0210004h0006, 16fk0210115h0001, 16bm0704007h0001]
- Grants-in-Aid for Scientific Research [16J05987, 15H02369, 16K18975] Funding Source: KAKEN
Ask authors/readers for more resources
During liver development, hepatoblasts and liver non-parenchymal cells (NPCs) such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) constitute the liver bud where they proliferate and differentiate. Accordingly, we reasoned that liver NPCs would support the maturation of hepatocytes derived from human induced pluripotent stem cells (hiPSCs), which usually exhibit limited functions. We found that the transforming growth factor b and Rho signaling pathways, respectively, regulated the proliferation and maturation of LSEC and HSC progenitors isolated from mouse fetal livers. Based on these results, we have established culture systems to generate LSECs and HSCs from hiPSCs. These hiPSC-derived NPCs exhibited distinctive phenotypes and promoted self-renewal of hiPSC-derived liver progenitor cells (LPCs) over the long term in the two-dimensional culture system without exogenous cytokines and hepatic maturation of hiPSC-derived LPCs. Thus, a functional human liver model can be constructed in vitro from the LPCs, LSECs, and HSCs derived from hiPSCs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available