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.

• 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

• MeSH
• játra diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• nemoci jater * farmakoterapie   MeSH
• nežádoucí účinky léčiv prevence a kontrola   MeSH
• Check Tag
• lidé MeSH

• MeSH
• chronická nemoc MeSH
• hojení ran * MeSH
• kočky MeSH
• koně MeSH
• nemoci nohy (od hlezna dolů) terapie   veterinární   MeSH
• otitis externa terapie   veterinární   MeSH
• plazmové plyny * terapeutické užití   MeSH
• pododermatitida terapie   MeSH
• psi MeSH
• výsledek terapie MeSH
• zánět terapie   veterinární   MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

• MeSH
• hojení ran * MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• plazmové plyny * terapeutické užití   MeSH
• rány a poranění terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH