Hepregen Peer-Reviewed Publications

General Technology
DMPK
Safety
Infectious Diseases

General Technology

Stem cell-derived liver cells for drug testing and disease modeling.
Davidson MD1, Ware BR1, Khetani SR2.   2015 May;19(106):349-58.
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The application of engineered liver tissues for novel drug discovery
Lin C1, Ballinger KRKhetani SR  2015 May;10(5):519-40. doi: 10.1517/17460441.2015.1032241. Epub 2015 Apr 3.
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Microengineered Liver Tissues for Drug Testing
Khetani SR1, Berger DR2, Ballinger KR3, Davidson MD2, Lin C2, Ware BR2.
 2015 Jun;20(3):216-250. Epub 2015 Jan 23. |
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Prediction of drug-induced liver injury in micropatterned co-cultures
containing iPSC-derived human hepatocytes. 
Brenton R. Ware, Dustin R. Berger, and Salman R. Khetani. ToxSci Advance Access published February 24, 2015
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Hormone and Drug-Mediated Modulation of Glucose Metabolism in a Microscale Model of the Human Liver. Matthew D. Davidson, BS(1), Michael Lehrer, BS(2), and Salman R. Khetani, PhD(1,3) Tissue Eng Part C Methods. 2014 Dec 17. [Epub ahead of print]
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Enhancing the Functional Maturity of iPSC-Derived Human Hepatocytes via
Controlled Presentation of Cell-Cell Interactions In Vitro.  Dustin R. Berger, Brenton R. Ware, Matthew D. Davidson, Samuel R. Allsup, and Salman R. Khetani.  Hepatology 2014 Nov 25. doi: 10.1002/hep.27621. [Epub ahead of print]
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Long-Term Stability of Primary Rat Hepatocytes in Micropatterned Co-Cultures. Okechukwu Ukairo, Chitra Kanchagar, Amanda Moore, Julianne Shi, Jeannemarie Gaffney, Simon Aoyama, Kelly Rose, Stacy Krzyzewski, Jack McGeehan, Melvin E. Andersen, Salman R. Khetani, Edward L. LeCluyse. Journal of Biochemical and Molecular Toxicology, Vol. 27(3), p 204–212,(2013).
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Microscale Culture of Human Liver Cells for Drug Development. Khetani SR, Bhatia SN.  Nat Biotechnol. Vol. 26(1), p. 120-126 (2008).
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Micromechanical Control of Cell-Cell Interactions. Elliot E. Hui and Sangeeta N. Bhatia. Proc Natl Acad Sci U S A, Vol. 104, No. 14, p 5722-5726 (2007).
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Engineering Tissues for In Vitro Applications. Salman R. Khetani and Sangeeta N. Bhatia. Current Opinion in Biotechnology, Vol. 17, p 524-531 (2006).
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Exploring Interactions Between Rat Hepatocytes and Nonparenchymal Cells Using Gene Expression Profiling. Khetani SR, Szulgit G, Del Rio JA, Barlow C, Bhatia SN.  Hepatology Vol. 40(3), p. 545–554 (2004).
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Effect of cell– cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells. Bhatia, S. N., Balis, U. J.,Yarmush, M. L., Toner, M. FASEB J., Vol. 13, p 1883-1900, (1999).
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Controlling Cell Interactions by Micropatterning in Co-Cultures: Hepatocytes and 3T3 Fibroblasts. Sangeeta N. Bhatia, Martin L. Yarmush, and Mehmet Toner. Journal of Biomedical Materials Research, Vol. 34, 189-199 (1997).
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DMPK

Metabolic Profiling of Human Long-Term Liver Models and Hepatic Clearance Predictions from In Vitro Data Using Nonlinear Mixed-Effects Modeling. Kratochwil NA1, Meille C2, Fowler S2, Klammers F2, Ekiciler A2, Molitor B2, Simon S2, Walter I2, McGinnis C2, Walther J2, Leonard B2, Triyatni M2, Javanbakht H2, Funk C2, Schuler F2, Lavé T2, Parrott NJ2. AAPS J. 2017 Jan 3. doi: 10.1208/s12248-016-0019-7. Read More

Advances in high-resolution MS and hepatocyte models solve a long-standing metabolism challenge: the loratadine story. Aratyn-Schaus Y1, Ramanathan R2. Bioanalysis. 2016 Aug;8 (16):1645-62. doi: 10.4155/bio-2016-0094. Epub 2016 Jul 27. Read More

Nuclear Receptor-Mediated Gene Expression Changes in a Human Hepatic Micropatterned Coculture Model After Treatment with Hepatotoxic Compounds. Rose Kelly, Wolf Kristina K., Ukairo Okechukwu, Moore Amanda, Gaffney Jeannemarie, Bradford Blair U., Wetmore Barbara A., Andersen Melvin E., and LeCluyse Edward L. Applied In Vitro Toxicology. March 2016, 2(1): 8-16. doi:10.1089/aivt.2015.0024. Read More

Evaluation of the Interplay between Uptake Transport and CYP3A4 Induction in Micropatterned Cocultured Hepatocytes. Moore A1, Chothe PP1, Tsao H1, Hariparsad N2. Drug Metab Dispos. 2016 Dec;44(12):1910-1919. Epub 2016 Sep 21. Read More

Determination of a degradation constant for CYP3A4 by direct suppression of mRNA in a novel human hepatocyte model, HepatoPac. Ramsden D1Zhou J2Tweedie DJ3.  2015 Jun 15. pii: dmd.115.065326. [Epub ahead of print]
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Application of Micropatterned Cocultured Hepatocytes to Evaluate the Inductive Potential and Degradation Rate of Major Xenobiotic Metabolizing Enzymes. Dixit V1, Moore A2, Tsao H2, Hariparsad N2 2016 Feb;44(2):250-61. doi: 10.1124/dmd.115.067173. Epub 2015 Dec 9. Read More

Application of a Micropatterned Cocultured Hepatocyte System To Predict Preclinical and Human-Specific Drug Metabolism. Ballard TE1, Wang S2, Cox LM2, Moen MA2, Krzyzewski S2, Ukairo O2, Obach RS2. 2016 Feb;44(2):172-9. doi: 10.1124/dmd.115.066688. Epub 2015 Nov 25. Read More

Prediction of Drug Clearance and Drug-Drug Interactions in Microscale Cultures of Human Hepatocytes. Lin C1, Shi J1, Moore A1, Khetani SR2Drug Metab Dispos. 2016 Jan;44(1):127-36. doi: 10.1124/dmd.115.066027. Epub 2015 Oct 9. Read More

Altered CYP2C9 Activity Following Modulation of CYP3A4 Levels in Human Hepatocytes: An Example of Protein-protein Interactions. Diane Ramsden, Donald J. Tweedie, Tom S.Chan, and Timothy S. Tracy Drug Metab and Dispos. Early Access. August 2014.
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Bridging in vitro and in vivo metabolism and transport of faldaprevir in human using a novel cocultured human hepatocyte system, HepatoPac®.   Diane Ramsden, Donald J. Tweedie, Tom S. Chan, Mitchell E. Taub, and Yongmei Li Drug Metab and Dispos. Early Access. December 2013.
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Generating an IVIVC for metabolism and liver enrichment of an HCV drug, faldaprevir, using a rat hepatocyte model (HepatoPac®).   Diane Ramsden, Donald J. Tweedie, Roger St. George, Lin-Zhi Chen, and Yongmei Li. Drug Metab and Dispos. Early Access. December 2013.
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Enzyme-transporter interplay in the formation and clearance of abundant metabolites of faldaprevir found in excreta but not in circulation.   Yongmei Li, Jin Zhou, Diane Ramsden, Mitchell E. Taub, Drané O'Brien, Jun Xu, Carl A. Busacca, Nina Gonnella, and Donald J. Tweedie. Drug Metab and Dispos. Early Access. December 2013.
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Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac®. Tom S. Chan, Hongbin Yu, Amanda Moore, Salman Khetani and Donald Tweedie. Drug Metab and Dispos. Vol. 41(12), p 2024-2032 (2013).
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Assessment of a micropatterned hepatocyte coculture system to generate major human excretory and circulating drug metabolites.
Wendy WeiWei Wang, Salman R. Khetani, Stacy Krzyzewski, David Duignan and R. Scott Obach.  Drug Metabolism and Disposition, Vol. 38(10), p 1900-1905 (2010).
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Safety

Establishment of a Hepatocyte-Kupffer Cell Co-Culture Model for
Assessment of Proinflammatory Cytokine Effects on Metabolizing Enzymes
and Drug Transporters.
 Theresa V Nguyen, Okechukwu Ukairo, Salman R Khetani, Michael McVay, Chitra Kanchagar, Wolfgang Seghezzi, Gulesi Ayanoglu, Onyi Irrechukwu, Raymond Evers. DMD Fast Forward. Published on March 4, 2015 as DOI: 10.1124/dmd.114.061317
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A Micropatterned Hepatocyte Coculture Model for Assessment of Liver Toxicity Using High-Content Imaging Analysis. O. Joseph Trask, Jr., Amanda Moore, and Edward L. LeCluyse. Assay Drug Dev Technol., Vol. 12 (1), p 16-27, (2014).
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Long-Term Stability of Primary Rat Hepatocytes in Micropatterned Cocultures. Okechukwu Ukairo, Chitra Kanchagar, Amanda Moore, Julianne Shi, Jeannemarie Gaffney, Simon Aoyama, Kelly Rose, Stacy Krzyzewski, Jack McGeehan, Melvin E. Andersen, Salman R. Khetani, and Edward L. LeCluyse. J Biochem Mol Toxicol. 2013 Mar;27(3):204-12. doi: 10.1002/jbt.21469. Epub 2013 Jan 11.
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Bioactivation and Toxicity of Acetaminophen in a Rat Hepatocyte Micropatterned Coculture System. Okechukwu Ukairo, Michael McVay, Stacy Krzyzewski, Simon Aoyama, Kelly Rose, Melvin E. Andersen, Salman R. Khetani, Edward L. LeCluyse. Journal of Biochemical and Molecular Toxicology. Early Release Epub, August 5, 2013.
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The Use of Micropatterned Co-Cultures to Detect Compounds that Cause Drug induced Liver Injury in Humans. Salman R. Khetani, Chitra Kanchagar, Okechukwu Ukairo, Stacy Krzyzewski, Amanda Moore, Julianne Shi, Simon Aoyama, Michael Aleo and Yvonne Will. Toxicol. Sci. 132 (1): p 107-117, (2013).
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Infectious Diseases

Modeling Host Interactions with Hepatitis B Virus Using Primary and Induced Pluripotent Stem Cell-Derived Hepatocellular Systems. Amir Shlomaia, Robert E. Schwartzb, Vyas Ramananc, Ankit Bhattaa, Ype P. de Jonga, Sangeeta N. Bhatia, and Charles M. Ricea. Proc Natl Acad Sci U S A., Published online before print August 4, 2014, doi: 10.1073/pnas.1412631111 
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A Microscale Human Liver Platform that Supports the Hepatic Stages of Plasmodium falciparum and vivax.  Sandra March, Shengyong Ng, Soundarapandian Velmurugan, Ani Galstian, Jing Shan, David J. Logan, Anne E. Carpenter, David Thomas, B. Kim Lee Sim, Maria M. Mota, Stephen L. Hoffman,  and Sangeeta N. Bhatia.  Cell Host & Microbe, Vol. 14, p 104–115, (2013).
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Persistent Hepatitis C Virus Infection in Microscale Primary Human Hepatocyte Cultures.  Ploss A, Khetani SR, Jones CT, Syder AJ, Trehan K, Gaysinskaya VA, Mu K, Ritola K, Rice CM, Bhatia SN.   Proc Natl Acad Sci U S A, Vol. 107(7), p 3141-3145 (2010).
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