Open Access
Identification of small molecules for human hepatocyte expansion and iPS differentiation
Jing Shan,Nathan T. Ross,David J. Logan,David Thomas,Stephen A. Duncan,Trista E. North,Wolfram Goessling,Anne E. Carpenter,Robert E. Schwartz,Sangeeta N. Bhatia +9 more
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TLDR
A high-throughput screening platform for primary human hepatocytes is developed to identify small molecules in two different classes that can be used to generate renewable sources of functional human liver cells in vitro.Abstract:
Broad Institute of MIT and Harvard (Scientific Planning and Allocation of Resources Committee Grant)read more
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Microfluidic organs-on-chips
TL;DR: A microfluidic cell culture device created with microchip manufacturing methods that contains continuously perfused chambers inhabited by living cells arranged to simulate tissue- and organ-level physiology has great potential to advance the study of tissue development, organ physiology and disease etiology.
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Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
Meritxell Huch,Helmuth Gehart,Ruben van Boxtel,Karien Hamer,Francis Blokzijl,Monique M A Verstegen,Ewa Ellis,Martien van Wenum,Sabine A. Fuchs,Joep de Ligt,Marc van de Wetering,Nobuo Sasaki,Susanne J. Boers,Hans Kemperman,Jeroen de Jonge,Jan N. M. IJzermans,Edward E. S. Nieuwenhuis,Ruurdtje Hoekstra,Stephen C. Strom,Robert R G Vries,Luc J. W. van der Laan,Edwin Cuppen,Hans Clevers +22 more
TL;DR: Conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy.
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A liver-on-a-chip platform with bioprinted hepatic spheroids.
Nupura S. Bhise,Vijayan Manoharan,Vijayan Manoharan,Solange Massa,Solange Massa,Solange Massa,Ali Tamayol,Ali Tamayol,Masoumeh Ghaderi,Masoumeh Ghaderi,Mario Miscuglio,Mario Miscuglio,Qi Lang,Qi Lang,Yu Shrike Zhang,Yu Shrike Zhang,Su Ryon Shin,Su Ryon Shin,Giovanni Calzone,Giovanni Calzone,Nasim Annabi,Nasim Annabi,Thomas Shupe,Colin E. Bishop,Anthony Atala,Mehmet R. Dokmeci,Mehmet R. Dokmeci,Ali Khademhosseini,Ali Khademhosseini,Ali Khademhosseini +29 more
TL;DR: Treatment with 15 mM acetaminophen induced a toxic response in the hepatic construct that was similar to published studies on animal and other in vitro models, thus providing a proof-of-concept demonstration of the utility of this liver-on-a-chip platform for toxicity assessment.
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Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes
Melissa A. Baxter,Sarah L. Withey,Sean Harrison,Charis-Patricia Segeritz,Charis-Patricia Segeritz,Fang Zhang,Rebecca Atkinson-Dell,Cliff Rowe,Cliff Rowe,Dave T. Gerrard,Rowena Sison-Young,Roz Jenkins,Joanne Henry,Andrew Berry,Lisa Mohamet,Marie Best,Stephen W. Fenwick,Hassan Malik,Neil R. Kitteringham,Christopher E. Goldring,Karen Piper Hanley,Ludovic Vallier,Ludovic Vallier,Neil A. Hanley,Neil A. Hanley +24 more
TL;DR: In this article, the authors generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes, and found that HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype.
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Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems
Amir Shlomai,Robert E. Schwartz,Vyas Ramanan,Ankit Bhatta,Ype P. de Jong,Sangeeta N. Bhatia,Charles M. Rice +6 more
TL;DR: It is reported that micropatterned cocultures of primary human hepatocytes with stromal cells (MPCCs) reliably support productive HBV infection, and infection can be enhanced by blocking elements of the hepatocyte innate immune response associated with the induction of IFN-stimulated genes.
References
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Humanized mice with ectopic artificial liver tissues.
Alice A. Chen,David Thomas,Luvena L. Ong,Robert E. Schwartz,Todd R. Golub,Sangeeta N. Bhatia +5 more
TL;DR: M mice with HEALs are used to predict the disproportionate metabolism and toxicity of “major” human metabolites using multiple routes of administration and monitoring to enable manufacturing of reproducible in vivo models for diverse drug development and research applications.
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PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury
Trista E. North,I. Ramesh Babu,Lea M. Vedder,Allegra M. Lord,John S. Wishnok,Steven R. Tannenbaum,Leonard I. Zon,Wolfram Goessling +7 more
TL;DR: Zebrafish can be used as a clinically relevant toxicological model amenable to the identification of additional therapeutics and biomarkers of APAP injury; the data suggest combinatorial PGE2 and NAC treatment would be beneficial for patients with APAP-induced liver damage.
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Stimulation of growth of primary cultured adult rat hepatocytes without growth factors by coculture with nonparenchymal liver cells.
TL;DR: The results suggest that DNA synthesis in parenchymal hepatocytes is stimulated not only by various humoral growth factors but also by cell-cell interaction between paren chymal and nonparenchymic hepatocytes, possibly endothelial cells, important in repair of liver damage and liver regeneration.
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The current status of primary hepatocyte culture.
TL;DR: The culture conditions for the proliferation and differentiation of primary hepatocytes are described and the small hepatocytes, especially their roles in liver growth are discussed.
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Multiple cell cycles occur in rat hepatocytes cultured in the presence of nicotinamide and epidermal growth factor
TL;DR: In this paper, multiple rounds of cell division were induced in primary cultures of rat hepatocytes in serum-free medium containing 10 mmol/L nicotinamide and 10 ng epidermal growth factor/ml.