期刊
STEM CELL REPORTS
卷 5, 期 6, 页码 1250-1262出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2015.10.016
关键词
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资金
- UK Regenerative Medicine Platform [MR/K026666/1, MR/L022974/1]
- MRC Ph.D. studentships
- China scholarship
- MRC [G0801057]
- BBSRC/TSB [BB/J021636/1]
- Wellcome Trust [102839/Z/13/Z]
- European Union [266838]
- NOTOX [267038]
- BMBF (German Federal Ministry of Education and Research) [0313854]
- Wellcome Trust [102839/Z/13/Z] Funding Source: Wellcome Trust
- BBSRC [BB/J021636/1] Funding Source: UKRI
- MRC [G0801057, MR/L022974/1, MR/K026666/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J021636/1] Funding Source: researchfish
- Medical Research Council [MR/K026666/1, 1202171, 1543095, G0801057, MR/L022974/1] Funding Source: researchfish
Stem cell-derived somatic cells represent an unlimited resource for basic and translational science. Although promising, there are significant hurdles that must be overcome. Our focus is on the generation of the major cell type of the human liver, the hepatocyte. Current protocols produce variable populations of hepatocytes that are the product of using undefined components in the differentiation process. This serves as a significant barrier to scale-up and application. To tackle this issue, we designed a defined differentiation process using recombinant laminin substrates to provide instruction. We demonstrate efficient hepatocyte specification, cell organization, and significant improvements in cell function and phenotype. This is driven in part by the suppression of unfavorable gene regulatory networks that control cell proliferation and migration, pluripotent stem cell self-renewal, and fibroblast and colon specification. We believe that this represents a significant advance, moving stem cell-based hepatocytes closer toward biomedical application.
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