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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease.
Kelly R. Stevens,Kelly R. Stevens,Margaret A. Scull,Vyas Ramanan,Chelsea L. Fortin,Chelsea L. Fortin,Ritika Chaturvedi,Kristin A. Knouse,Kristin A. Knouse,Jing W. Xiao,Canny Fung,Teodelinda Mirabella,Amanda X. Chen,Margaret McCue,Michael T. Yang,Heather E. Fleming,Kwanghun Chung,Ype P. de Jong,Ype P. de Jong,Christopher S. Chen,Christopher S. Chen,Charles M. Rice,Sangeeta N. Bhatia +22 more
TL;DR: Tissue seeds containing patterned human primary hepatocytes, endothelial cells, and stromal cells in a degradable hydrogel expanded more than 50-fold over the course of 11 weeks in mice with injured livers, demonstrating the utility of this system for probing the impact of multicellular geometric architecture on tissue expansion in response to liver injury.
Journal ArticleDOI
Long-term culture and expansion of primary human hepatocytes
Gahl Levy,David Bomze,Stefan Heinz,Sarada Devi Ramachandran,Astrid Noerenberg,Merav Cohen,Oren Shibolet,Ella H. Sklan,Joris Braspenning,Yaakov Nahmias +9 more
TL;DR: It is shown that E6 and E7 expression upregulates the OSM receptor gp130 and that OSM stimulation induces hepatocytes to expand for up to 40 population doublings, producing 1013 to 1016 cells from a single human hepatocyte isolate.
Journal ArticleDOI
Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens
Sandra March,Sandra March,Vyas Ramanan,Kartik Trehan,Shengyong Ng,Ani Galstian,Ani Galstian,Nil Gural,Margaret A. Scull,Amir Shlomai,Maria M. Mota,Heather E. Fleming,Salman R. Khetani,Charles M. Rice,Sangeeta N. Bhatia +14 more
TL;DR: In this article, the authors developed micropatterned cocultures (MPCCs), which consist of primary human hepatocytes organized into 2D islands that are surrounded by supportive fibroblast cells.
Journal ArticleDOI
Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics.
Sabine U. Vorrink,Shahid Ullah,Staffan Schmidt,Jatin Nandania,Vidya Velagapudi,Olof Beck,Magnus Ingelman-Sundberg,Volker M. Lauschke +7 more
TL;DR: The 3D spheroid system is metabolically stable and constitutes a suitable model for in vitro studies of long‐term drug metabolism and pharmacokinetics, as revealed by a combination of targeted and untargeted metabolomics.
Journal ArticleDOI
Microengineered Liver Tissues for Drug Testing
Salman R. Khetani,Dustin R. Berger,Kimberly R. Ballinger,Matthew D. Davidson,Christine Lin,Brenton R. Ware +5 more
TL;DR: The major trends, challenges, and opportunities associated with development and implementation of engineered liver models created from primary cells, cell lines, and stem cell–derived hepatocyte-like cells are reviewed.
References
More filters
Journal ArticleDOI
CellProfiler: image analysis software for identifying and quantifying cell phenotypes
Anne E. Carpenter,Thouis R. Jones,Michael R. Lamprecht,Colin Clarke,In Han Kang,Ola Friman,David A. Guertin,Joo Han Chang,Robert A. Lindquist,Jason Moffat,Polina Golland,David M. Sabatini +11 more
TL;DR: The first free, open-source system designed for flexible, high-throughput cell image analysis, CellProfiler is described, which can address a variety of biological questions quantitatively.
Journal ArticleDOI
Global epidemiology of hepatitis C virus infection
TL;DR: Because there is no vaccine and no post-exposure prophylaxis for HCV, the focus of primary prevention efforts should be safer blood supply in the developing world, safe injection practices in health care and other settings, and decreasing the number of people who initiate injection drug use.
Journal Article
Liver regeneration : Frontiers in medicine: Regeneration
TL;DR: This review attempts to integrate the findings of the last three decades and looks toward clues as to the nature of the causes that trigger this fascinating organ and cellular response.
Genome sequence of the Brown Norway rat yields insights into mammalian evolutionRat Genome Sequencing Project ConsortiumNature200442849352115057822
Richard A. Gibbs,George M. Weinstock,Michael L. Metzker,Donna M. Muzny,Erica Sodergren,Steven E. Scherer,Graham R. Scott,David Steffen,Kim C. Worley,Paula E. Burch,Geoffrey Okwuonu,Sandra Hines,Lora Lewis,C. DeRamo,Oliver Delgado,S. Dugan Rocha,George Miner,Margaret Morgan,Alicia Hawes,Rachel Gill,Robert A. Holt,Mark Raymond Adams,Peter G. Amanatides,H. Baden Tillson,Mary Barnstead,Soo H. Chin,Cheryl A. Evans,Steve Ferriera,Carl Fosler,A. Glodek,Gu Zp,D. Jennings,Cheryl L. Kraft,T. Nguyen,Cynthia Pfannkoch,Cynthia Sitter,Granger G. Sutton,J. C. Venter,Trevor Woodage,Douglas Smith,H. M. Lee,Erik Gustafson,Patrick Cahill,A. Kana,L. Doucette Stamm,Keith Weinstock,Kim Fechtel,Robert B. Weiss,Diane M. Dunn,Eric D. Green,Robert W. Blakesley,Gerard G. Bouffard,P. J. De Jong,Kazutoyo Osoegawa,Zhu Bl,Marco A. Marra,Jacqueline E. Schein,Ian Bosdet,Chris Fjell,Steven J.M. Jones,Martin Krzywinski,Carrie Mathewson,Asim Sarosh Siddiqui,Natasja Wye,John Douglas Mcpherson,Zhao Sy,Claire M. Fraser,Jyoti Shetty,Sofiya Shatsman,Keita Geer,Chen Yx,S. Abramzon,William C. Nierman,Paul Havlak,Rui Chen,K. J. Durbin,Amy Egan,Ren Yr,Xing Zhi Song,Li Bs,Yue Liu,Xiang Qin,Simon Cawley,Austin J. Cooney,Lisa M. D'Souza,Kirt Martin,Jia Qian Wu,M. L. Gonzalez Garay,Andrew R. Jackson,K. J. Kalafus,Michael P. McLeod,Aleksandar Milosavljevic,D. Virk,A. Volkov,David A. Wheeler,Zhang Zd,Jeffrey A. Bailey,Evan E. Eichler,Eray Tüzün,Ewan Birney,Emmanuel Mongin,A. Ureta Vidal,C. Woodwark,Evgeny M. Zdobnov,Peer Bork,Mikita Suyama,David Torrents,Marina Alexandersson,Barbara J. Trask,Janet M. Young,Hui Huang,Wang Hj,Xing Hm,Sue Daniels,Darryl Gietzen,Jeanette Schmidt,K. Stevens,Ursula Vitt,Jim Wingrove,Francisco Camara,M. Mar Albà,Josep F. Abril,Roderic Guigó,Arian F.A. Smit,Inna Dubchak,Edward M. Rubin,Olivier Couronne,Alexander Poliakov,Norbert Hubner,Detlev Ganten,C. Goesele,Oliver Hummel,Thomas Kreitler,Young-Ae Lee,Jan Monti,Herbert Schulz,Heike Zimdahl,Heinz Himmelbauer,Hans Lehrach,Howard J. Jacob,Susan Bromberg,J. Gullings Handley,M. I. Jensen Seaman,Anne E. Kwitek,Jozef Lazar,Dean Pasko,Peter J. Tonellato,Simon N. Twigger,Chris P. Ponting,Jose M. Duarte,Stephen Rice,Leo Goodstadt,Scott A. Beatson,Richard D. Emes,Eitan E. Winter,Caleb Webber,Petra Brandt,Gerald Nyakatura,M. Adetobi,Francesca Chiaromonte,Laura Elnitski,Pallavi Eswara,Ross C. Hardison,Hou Mm,Diana L. Kolbe,Kateryna D. Makova,Webb Miller,Anton Nekrutenko,Cathy Riemer,Scott Schwartz,James Taylor,Shan Yang,Yi Zhang,Klaus Lindpaintner,T. D. Andrews,Mario Caccamo,Michele Clamp,Laura Clarke,V. Curwen,Richard Durbin,Eduardo Eyras,Stephen M. J. Searle,Gregory M. Cooper,Serafim Batzoglou,Michael Brudno,Arend Sidow,Eric A. Stone,Bret A. Payseur,Guillaume Bourque,C. Lopez Otin,Xose S. Puente,Kushal Chakrabarti,Sourav Chatterji,Colin N. Dewey,Lior Pachter,Nicolas Bray,Von Bing Yap,Anat Caspi,G. Tesler,Pavel A. Pevzner,David Haussler,Krishna M. Roskin,Robert Baertsch,Hiram Clawson,Terrence S. Furey,Angie S. Hinrichs,Donna Karolchik,W. J. Kent,Kate R. Rosenbloom,Heather Trumbower,M. Weirauch,David Neil Cooper,Peter D. Stenson,Bin Ma,Michael R. Brent,Manimozhiyan Arumugam,David Shteynberg,Richard R. Copley,Martin S. Taylor,Harold Riethman,Uma Mudunuri,Jane Peterson,Mark S. Guyer,Adam Felsenfeld,Susan Old,Stephen C. Mockrin,Francis S. Collins +226 more
Abstract: The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality ‘draft’ covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
Journal ArticleDOI
Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo
Evert Kroon,Laura Martinson,Kuniko Kadoya,Anne G. Bang,Olivia Kelly,Susan Eliazer,Holly Y. Young,Mike Richardson,Nora G. Smart,Justine J Cunningham,Alan D. Agulnick,Kevin A. D'Amour,Melissa K. Carpenter,Emmanuel E. Baetge +13 more
TL;DR: It is shown that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice, and it is demonstrated that implantation of hES cell–derived pancreaticEndoderm protects against streptozotocin-induced hyperglycemia.