Recombinant Laminins Drive the Differentiation and Self-Organization of hESC-Derived Hepatocytes
| Autor: | Jan G. Hengstler, Katherine Cameron, Marcus J. Lyall, Patricio Godoy, Yu Wang, Dagmara Szkolnicka, Stuart J. Forbes, Baltasar Lucendo-Villarin, G Campos, Wolfgang Schmidt-Heck, David C. Hay, Nicola Bates, Rosanne Tan, Susan J. Kimber |
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| Rok vydání: | 2015 |
| Předmět: |
Resource
Cell type Somatic cell Cellular differentiation Cell Cell Culture Techniques Biology Biochemistry Cell Line 03 medical and health sciences 0302 clinical medicine Genetics medicine Humans Gene Regulatory Networks Induced pluripotent stem cell lcsh:QH301-705.5 Embryonic Stem Cells Cell Proliferation 030304 developmental biology 0303 health sciences lcsh:R5-920 Genome Human Cell growth Cell Differentiation Cell Biology Recombinant Proteins Cell biology medicine.anatomical_structure lcsh:Biology (General) Cell culture 030220 oncology & carcinogenesis Immunology Hepatocytes Laminin Stem cell lcsh:Medicine (General) Developmental Biology |
| Zdroj: | Cameron, K, Tan, R, Schmidt-Heck, W, Campos, G, Lyall, M J, Wang, Y, Lucendo-Villarin, B, Szkolnicka, D, Bates, N, Kimber, S J, Hengstler, J G, Godoy, P, Forbes, S J & Hay, D C 2015, ' Recombinant Laminins Drive the Differentiation and Self-Organization of hESC-Derived Hepatocytes ', Stem Cell Reports, vol. 5, no. 6, pp. 1250–1262 . https://doi.org/10.1016/j.stemcr.2015.10.016 Stem Cell Reports, Vol 5, Iss 6, Pp 1250-1262 (2015) Stem Cell Reports |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2015.10.016 |
| Popis: | Summary 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. Highlights • We designed a hepatocyte differentiation process under defined conditions • The hepatocyte phenotype is improved and stabilized on two laminin isoforms • Laminin-supported differentiation suppresses inappropriate gene networks • Laminin surfaces deliver hepatocytes with greater similarity to adult hepatocytes In this article, Hay and colleagues demonstrate that hepatocyte production is possible under defined conditions with GMP-grade hESC lines. The use of recombinant laminins significantly improved the stem cell-derived hepatocyte phenotype, which was closer in nature to primary adult hepatocytes. |
| Databáze: | OpenAIRE |
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