Development of liver microtissues with functional biliary ductular network.

Autor: Hafiz EOA; Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Shriners Hospitals for Children in Boston, Boston, Massachusetts, USA.; Electron Microscopy Research Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt., Bulutoglu B; Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Shriners Hospitals for Children in Boston, Boston, Massachusetts, USA., Mansy SS; Electron Microscopy Research Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt., Chen Y; Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Shriners Hospitals for Children in Boston, Boston, Massachusetts, USA., Abu-Taleb H; Immunology and Therapeutic Evaluation Department, TBRI, Giza, Egypt., Soliman SAM; Pathology Department, Kasr Al Ainy, Faculty of Medicine, Cairo University, Giza, Egypt., El-Hindawi AAF; Pathology Department, Kasr Al Ainy, Faculty of Medicine, Cairo University, Giza, Egypt., Yarmush ML; Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Shriners Hospitals for Children in Boston, Boston, Massachusetts, USA., Uygun BE; Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Shriners Hospitals for Children in Boston, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Biotechnology and bioengineering [Biotechnol Bioeng] 2021 Jan; Vol. 118 (1), pp. 17-29. Date of Electronic Publication: 2020 Sep 14.
DOI: 10.1002/bit.27546
Abstrakt: Liver tissue engineering aims to create transplantable liver grafts that can serve as substitutes for donor's livers. One major challenge in creating a fully functional liver tissue has been to recreate the biliary drainage in an engineered liver construct through integration of bile canaliculi (BC) with the biliary ductular network that would enable the clearance of bile from the hepatocytes to the host duodenum. In this study, we show the formation of such a hepatic microtissue by coculturing rat primary hepatocytes with cholangiocytes and stromal cells. Our results indicate that within the spheroids, hepatocytes maintained viability and function for up to 7 days. Viable hepatocytes became polarized by forming BC with the presence of tight junctions. Morphologically, hepatocytes formed the core of the spheroids, while cholangiocytes resided at the periphery forming a monolayer microcysts and tubular structures extending outward. The spheroids were subsequently cultured in clusters to create a higher order ductular network resembling hepatic lobule. The cholangiocytes formed functional biliary ductular channels in between hepatic spheroids that were able to collect, transport, and secrete bile. Our results constitute the first step to recreate hepatic building blocks with biliary drainage for repopulating the whole liver scaffolds to be used as transplantable liver grafts.
(© 2020 Wiley Periodicals LLC.)
Databáze: MEDLINE
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