RRC ID 49345
著者 Koui Y, Kido T, Ito T, Oyama H, Chen SW, Katou Y, Shirahige K, Miyajima A.
タイトル An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells.
ジャーナル Stem Cell Reports
Abstract 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 β 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.
巻・号 9(2)
ページ 490-498
公開日 2017-8-8
DOI 10.1016/j.stemcr.2017.06.010
PII S2213-6711(17)30273-4
PMID 28757162
PMC PMC5549957
MeSH Activated-Leukocyte Cell Adhesion Molecule / metabolism Animals Biomarkers Cell Differentiation* / genetics Cells, Cultured Coculture Techniques Endothelial Cells / cytology Endothelial Cells / metabolism Fetus Gene Expression Profiling Hepatic Stellate Cells / cytology Hepatic Stellate Cells / metabolism Hepatocytes / cytology Hepatocytes / metabolism Humans Immunophenotyping Induced Pluripotent Stem Cells / cytology* Liver / cytology* Liver / metabolism Liver Regeneration Mice Phenotype
IF 6.032
引用数 36
リソース情報
ヒト・動物細胞 409B2(HPS0076) 454E2(HPS0077)