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Scalable production of tissue-like vascularized liver organoids from human PSCs
SP. Harrison, R. Siller, Y. Tanaka, ME. Chollet, ME. de la Morena-Barrio, Y. Xiang, B. Patterson, E. Andersen, C. Bravo-Pérez, H. Kempf, KS. Åsrud, O. Lunov, A. Dejneka, MC. Mowinckel, B. Stavik, PM. Sandset, E. Melum, S. Baumgarten, F. Bonanini,...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
Directory of Open Access Journals
od 1996
Free Medical Journals
od 1996
Nature Open Access
od 1996-03-01
PubMed Central
od 2008
Europe PubMed Central
od 2008
ProQuest Central
od 2000-03-01
Health & Medicine (ProQuest)
od 2000-03-01
Springer Nature OA/Free Journals
od 1996-03-01
- MeSH
- hepatocyty MeSH
- játra * MeSH
- kultivované buňky MeSH
- lidé MeSH
- myši MeSH
- organoidy * MeSH
- tkáňové inženýrství MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The lack of physiological parity between 2D cell culture and in vivo culture has led to the development of more organotypic models, such as organoids. Organoid models have been developed for a number of tissues, including the liver. Current organoid protocols are characterized by a reliance on extracellular matrices (ECMs), patterning in 2D culture, costly growth factors and a lack of cellular diversity, structure, and organization. Current hepatic organoid models are generally simplistic and composed of hepatocytes or cholangiocytes, rendering them less physiologically relevant compared to native tissue. We have developed an approach that does not require 2D patterning, is ECM independent, and employs small molecules to mimic embryonic liver development that produces large quantities of liver-like organoids. Using single-cell RNA sequencing and immunofluorescence, we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, and a population of resident macrophages: Kupffer cells. The organoids exhibit key liver functions, including drug metabolism, serum protein production, urea synthesis and coagulation factor production, with preserved post-translational modifications such as N-glycosylation and functionality. The organoids can be transplanted and maintained long term in mice producing human albumin. The organoids exhibit a complex cellular repertoire reflective of the organ and have de novo vascularization and liver-like function. These characteristics are a prerequisite for many applications from cellular therapy, tissue engineering, drug toxicity assessment, and disease modeling to basic developmental biology.
Department of Chemistry University of Oslo P O Box 1033 Blindern NO 0315 Oslo Norway
Department of Engineering Faculty of Science Durham University Durham DH1 3LE United Kingdom
Department of Forensic Sciences Oslo University Hospital Oslo Norway
Department of Haematology Oslo University Hospital Oslo Norway
Department of Immunology University of Oslo and Oslo University Hospital Oslo Norway
Department of Molecular Medicine Institute of Basic Medical Sciences University of Oslo Oslo Norway
Department of Pediatric Research Oslo University Hospital Oslo Norway
European Reference Network RARE LIVER Hamburg Germany
Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway
Mimetas Leiden The Netherlands
Research Institute of Internal Medicine Oslo University Hospital Oslo Norway
Citace poskytuje Crossref.org
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