Microfabricated Tissue Models Laboratory
SCHOLARLY PUBLICATIONS
MTM Lab is internationally recognized for contributions in tissue engineering, with an expanding repertoire of studying diverse types of mammalian cells and organs for various applications.
List of Services
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Engineered cocultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation
Grace E. Brown et al. ,Engineered cocultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation. Sci. Adv. 10, eadg1222 (2024). DOI: 10.1126/sciadv.adg1222
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Decellularized Liver Nanofibers Enhance and Stabilize the Long-Term Functions of Primary Human Hepatocytes In Vitro
Liu JS, Madruga LYC, Yuan Y, Kipper MJ, Khetani SR. Decellularized Liver Nanofibers Enhance and Stabilize the Long-Term Functions of Primary Human Hepatocytes In Vitro. Adv Healthc Mater. 2023 Jul;12(19):e2202302.
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A human iPSC-derived hepatocyte screen identifies compounds that inhibit production of Apolipoprotein B.
Liu JT, Doueiry C, Jiang YL, Blaszkiewicz J, Lamprecht MP, Heslop JA, Peterson YK, Carten JD, Traktman P, Yuan Y, Khetani SR, Twal WO, Duncan SA. A human iPSC-derived hepatocyte screen identifies compounds that inhibit production of Apolipoprotein B. Commun Biol. 2023 Apr 24;6(1):452.
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Engineered Platforms for Maturing Pluripotent Stem Cell-Derived Liver Cells for Disease Modeling
Yuan Y, Cotton K, Samarasekera D, Khetani SR. Engineered Platforms for Maturing Pluripotent Stem Cell-Derived Liver Cells for Disease Modeling. Cell Mol Gastroenterol Hepatol. 2023;15(5):1147-1160.
List of Services
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Engineered co-cultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation
Brown, G.*, Han, Y.*, Ly, O., Vanoye, C.G., George, A.L., Darbar, D.#, and Khetani, S.R.# Engineered co-cultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation. Under review. *These authors contributed equally. #Co-orresponding authors
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Reanalysis of Trichloroethylene and Tetrachloroethylene Metabolism to Glutathione Conjugates Using Human, Rat, and Mouse Liver in Vitro Models to Improve Precision in Risk Characterization
Valdiviezo, A., Brown, G.E., Michell, A.R., Trinconi, C.M., Bodke, V.V., Khetani, S.R., Luo, Y.S., Chiu, W.A., and Rusyn, I. Reanalysis of Trichloroethylene and Tetrachloroethylene Metabolism to Glutathione Conjugates Using Human, Rat, and Mouse Liver in Vitro Models to Improve Precision in Risk Characterization. Environmental Health Perspectives 130(11):117009 (2022)
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Polygodial, a sesquiterpene of Tasmanian pepper berry, activates apoptotic signaling in castration-resistant prostate cancer cell lines by inducing oxidative stress
Venkatesa, R., Hussein, M.A., Liu, J.S., Khetani, S.R., Kornienko, A., Munirathinam, G. Polygodial, a sesquiterpene of Tasmanian pepper berry, activates apoptotic signaling in castration-resistant prostate cancer cell lines by inducing oxidative stress. Cancers 14(21):5260 (2022)
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Engineered Matrix Microenvironments Reveal the Heterogeneity of Liver Sinusoidal Endothelial Cell Phenotypic Responses
Brougham-Cook, A., Monckton, C.P., Owen, D., Khetani, S.R., and Underhill, G. Engineered Matrix Microenvironments Reveal the Heterogeneity of Liver Sinusoidal Endothelial Cell Phenotypic Responses. APL Bioengineering 6:046102 (2022)
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Modulation of Human iPSC-derived Human Hepatocyte Phenotype Via Extracellular Matrix Microarrays
Monckton, C.P., Brougham-Cook, A., Underhill, G., and Khetani, S.R. Modulation of Human iPSC-derived Human Hepatocyte Phenotype Via Extracellular Matrix Microarrays. Acta Biomaterialia 153:216-230 (2022)
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LIGHT Enhanced Bispecific Antibody Armed T-cells to Treat Immunotherapy Resistant Colon Cancer
Qiao, G., Kone, L.B., Phillips, E.H., Lee, S.S., Brown, G.E., Khetani, S.R., Thakur, A., Lum, L.G., Prabhakar, B.S., and Maker, A.V. LIGHT Enhanced Bispecific Antibody Armed T-cells to Treat Immunotherapy Resistant Colon Cancer. Oncogene - doi: 10.1038/s41388-022-02209 (2022)
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Mature Patient Stem Cell-Derived Atrial Cardiomyocytes Unmask Ion Channel and Metabolic Defects in an NPPA Atrial Fibrillation Model
Ly, O., Brown, G., Chen, H., Hong, H., Wang, X., Han, Y., Arif, M., Sridhar, A., Maienschein-Cline, M., Chalazan, B., Ong, S., Abdelhady, K., Massad, M., Rizkallah, L., Rehman, J., Khetani, S.R.*, and Darbar, D.* Mature Patient Stem Cell-Derived Atrial Cardiomyocytes Unmask Ion Channel and Metabolic Defects in an NPPA Atrial Fibrillation Model. JCI Insight 7(7):e155640 (2022). *Co-corresponding authors
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The Role of Liver Zonation in Physiology, Regeneration, and Disease
Panday, R., Monckton, C.P., and Khetani, S.R. The Role of Liver Zonation in Physiology, Regeneration, and Disease. Seminars in Liver Disease 42(1):1-16 (2022)
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High Throughput Interrogation of Human Liver Stellate Cells Reveals Microenvironmental Regulation of Phenotype
Brougham-Cook, A., Jain, I., Kukla, D., Masood, F., Khetani, S., and Underhill, G. High Throughput Interrogation of Human Liver Stellate Cells Reveals Microenvironmental Regulation of Phenotype. Acta Biomaterialia 138:240-253 (2022)
2021
56. Monckton, C.P., Brougham-Cook, A., Kaylan, K., Underhill, G., and Khetani, S.R. Elucidating Extracellular Matrix and Stiffness Control of Primary Human Hepatocyte Phenotype Via Cell Microarrays. Advanced Materials Interfaces 8(22):2101284 (2021)
55. Monckton, C.P.*, Brown, G.E.*, and Khetani, S.R. The Latest Impact of Engineered Human Liver Platforms on Drug Development. APL Bioengineering 5(3):031506 (2021) *These authors contributed equally to this work
54. Rusyn, I., Arzuaga, X., Cattley, C., Corton, J.C., Ferguson, S.S., Godoy, P., Guyton, K.Z., Kaplowitz, N., Khetani, S.R., Roberts, R., Roth, R.A., and Smith, M.T. Key Characteristics of Human Hepatotoxicants as a Basis for Identification and Characterization of the Causes of Liver Toxicity. Hepatology - doi: 10.1002/hep.31999 (2021)
53. Kukla, D.A. and Khetani, S.R. Bioengineered Liver Models for Investigating Disease Pathogenesis and Regenerative Medicine. Seminars in Liver Disease - doi: 10.1055/s-0041-1731016 (2021)
52. Ly, O., Brown, G., Han, Y.D., Darbar, D., and Khetani, S.R. Bioengineering Approaches to Mature Induced Pluripotent Stem Cell Derived Atrial Cardiomyocytes to Model Atrial Fibrillation. Experimental Biology and Medicine - online ahead of print https://doi.org/10.1177/15353702211009146 (2021)
51. Ware, B.R.*, Liu, J.S.*, Monckton, C.P., Ballinger, K., and Khetani, S.R. Micropatterned Co-culture with 3T3-J2 Fibroblasts Enhances Hepatic Functions and Drug Screening Utility of HepaRG Cells. Toxicological Sciences 181(1):90-104 (2021). Cover article *These authors contributed equally to this work
2020
50. Khetani, S.R. Pluripotent Stem Cell-Derived Human Liver Organoids Enter the Realm of High-Throughput Drug Screening. Gastroenterology S0016-5085(20)35539-6. doi: 10.1053/j.gastro.2020.12.005. Online ahead of print (2020)
49. Davidson, M.D., Pickrell, J., and Khetani, S.R. Physiologically Inspired Culture Medium Prolongs the Lifetime and Insulin Sensitivity of Human Hepatocytes in Micropatterned Co-cultures. Toxicology 449:152662 (2020)
48. Kukla, D.A., Stoppel, W.L., Kaplan, D.L., and Khetani, S.R. Assessing the Compatibility of Primary Human Hepatocyte Culture Within Porous Silk Sponges. RSC Advances 10:37662–37674 (2020)
47. Kukla, D.A., Crampton, A.L., Wood, D.K.*, and Khetani, S.R.* Microscale Collagen and Fibroblast Interactions Enhance Primary Human Hepatocyte Functions in 3-Dimensional Models. Gene Expression – The Journal of Liver Research 20(1):1-18 (2020) *Co-corresponding authors
2019
46. Davidson, M.D., and Khetani, S.R. Intermittent Starvation Extends the Functional Lifetime of Primary Human Hepatocyte Cultures. Toxicological Sciences 174(2):266-277 (2019)
45. Underhill, G.H.*, and Khetani, S.R.* Emerging Trends in Modeling Liver Disease In Vitro. APL Bioengineering 3(4):040902 (2019) *Co-corresponding authors
44. Ware, B.R.*, Brown G.E.*, Soldatow, V.Y., LeCluyse, E.L., and Khetani, S.R. Long-term Engineered Cultures of Primary Mouse Hepatocytes for Strain and Species Comparison Studies During Drug Development. Gene Expression – The Journal of Liver Research 19(3):199-214 (2019) *These authors contributed equally to this work
2018
43. Underhill, G.H.*, and Khetani, S.R.* Advances in Engineered Human Liver Platforms for Drug Metabolism Studies. Drug Metabolism and Disposition 46(11):1626-1637 (2018) *Co-corresponding authors
42. Brown, G., and Khetani, S.R. Microfabrication of liver and heart tissues for drug development. Philos Trans R Soc Lond B Biol Sci. 373(1750), pii: 20170225 (2018)
2017
41. Underhill, G.H.*, and Khetani, S.R.* Bioengineered liver models for drug testing and cell differentiation studies. Cellular and Molecular Gastroenterology and Hepatology 5(3):426-439.e1 (2017) *Co-corresponding authors
40. Meseguer-Ripolles, J., Khetani, S.R., Blanco, J.G., Iredale, M., Hay, D.C. Pluripotent stem cell derived human tissue: platforms to evaluate drug metabolism and safety. The AAPS journal 20(1):20 (2017) [Erratum in: AAPS J. 2018 Feb 12;20(2):30]
39. Ware, B.R., Durham, M.J., Monckton, C.P., and Khetani, S.R. A cell culture platform to maintain long-term phenotype of primary human hepatocytes and endothelial cells. Cellular and Molecular Gastroenterology and Hepatology 5(3):187-207 (2017) -- Video Summary
38. Lin, C., Romero, R., Sorokina, L.V., Ballinger, K.R., Place, L.W., Kipper, M.J., and Khetani, S.R. A polyelectrolyte multilayer platform for investigating growth factor delivery modes in human liver cultures. Journal of Biomedical Materials Research – Part A 106(4):971-984 (2017)
37. Mosedale, M., Eaddy, J.S., Trask, O.J., Holman, N., Wolf, K.K., LeCluyse, E., Ware, B., Khetani, S.R., Lu, J., Brock, W.J., Roth, S.E., and Watkins, P.B. miR-122 release in exosomes precedes overt tolvaptan-induced necrosis in a primary human hepatocyte micropatterned coculture model. Toxicological Sciences 161(1):149-158 (2017)
36. Davidson, M.D., Kukla, D., and Khetani, S.R. Microengineered cultures containing human hepatic stellate cells and hepatocytes for drug development. Integrative Biology 9(8):662-677 (2017) (Featured on the journal cover)
35. Ware, B.R., Sunada, W., McVay, M., and Khetani, S.R. Exploring chronic drug effects on microengineered human liver cultures using global gene expression profiling. Toxicological Sciences 157(2):387-398 (2017) (Recommended by F1000Prime)
34. Lin, C., and Khetani, S.R. Micropatterned co-cultures of human hepatocytes and stromal cells for the assessment of drug clearance and drug-drug Interactions. Current Protocols in Toxicology 72:14.17.1-14.17.23 (2017)
2016
33. Lin, C. and Khetani, S.R. Advances in engineered liver models for investigating drug-induced liver injury. BioMed Research International 2016:1829148 (2016)
32. Ware, B.R., and Khetani, S.R. Engineered liver platforms for different phases of drug development. Trends in Biotechnology 35(2):172-183 (2016)
31. Neufeld, M.J., Ware, B.R., Lutzke, A., Khetani, S.R., and Reynolds, M.M. Water-stable metal-organic framework polymer composites compatible with human hepatocytes. ACS Applied Materials and Interfaces 8(30):19343-19352 (2016)
30. Wang, W., Lockwood, K., Boyd, L., Davidson, M., Movafaghi, S., Vahabi, H., Khetani, S.R., and Kota, A.K. Superhydrophobic coatings with edible materials. ACS Applied Materials and Interfaces 8(29):18664-18668 (2016)
29. Davidson, M.D., Ballinger, K.R., and Khetani, S.R. Long-term exposure to abnormal glucose levels alters drug metabolism pathways and insulin sensitivity in primary human hepatocytes. Scientific Reports 6:28178 (2016)
28. Lin, C., Shi, J., Moore, A., and Khetani, S.R. Prediction of drug clearance and drug-drug interactions in microscale cultures of human hepatocytes. Drug Metabolism and Disposition 44(1):127-136 (2016)
2015
27. March, S., Trehan, K., Ramanan, V., Ng, S., Galstian, A., Scull, M.A., Shlomai, A., Mota, M., Fleming, H.E., Khetani, S.R., Rice, C.M., and Bhatia, S.N. Micropatterned co-cultures of primary human hepatocytes for the study of hepatotropic pathogens. Nature Protocols 10(12):2027-2053 (2015)
26. Davidson, M.D.*, Ware, B.R.* and Khetani, S.R. Stem cell-derived liver cells for drug testing and disease modeling. Discovery Medicine 19(106):349-358 (2015). *These authors contributed equally
25. Lin, C*., Ballinger, K*., and Khetani, S.R. The application of engineered liver tissues for novel drug discovery. Expert Opinion on Drug Discovery 10(5):519-540 (2015). *These authors contributed equally
24. Nguyen, T., Ukairo, O., Khetani, S.R., McVay, M., Kanchagar, C., Seghezzi, W., Ayanoglu, G., Irrechukwu, O., and Evers, R. Establishment of a hepatocyte-Kupffer cell co-culture model for assessment of proinflammatory cytokine effects on metabolizing enzymes and drug transporters. Drug Metabolism and Disposition 43(5):774-785 (2015)
23. Ware, B., Berger, D., and Khetani, S.R. Prediction of drug-induced liver injury in micropatterned co-cultures containing iPSC-derived human hepatocytes. Toxicological Sciences 145(2):252-262 (2015)
22. Mitchell, A.M., Stone, A.E.L., Cheng, L., Ballinger, K., Edwards, M., Stoddard, M., Li, H., Golden-Mason, L., Shaw, G.M., Khetani, S.R, and Rosen, H.R. Transmitted/founder hepatitis C viruses induce cell type- and genotype-specific differences in innate signaling within the liver. mBio 6(2):e02510 (2015)
21. Khetani, S.R., Ballinger, K.R., Berger, D.R., Davidson, M.D., Lin, C., and Ware, B. Microengineered liver tissues for drug testing. Journal of Laboratory Automation 20(3):216-250 (2015)
20. Davidson, M.D., Lehrer, M., and Khetani, S.R. Hormone and drug-mediated modulation of glucose metabolism in a microscale model of the human liver. Tissue Engineering, Part C Methods 21(7):716-725 (2015)
19. Berger, D., Ware, B., Davidson, M., Allsup, S., and Khetani, S.R. Enhancing the functional maturity of iPSC-derived human hepatocytes via controlled presentation of cell-cell interactions in vitro. Hepatology 61(4):1370-1381 (2015)
2014
18. Giugliano, S., Golden-Mason, L., Dobrinskikh, E., Stone, A., Kriss, M., Soto-Guiterrez, A., Mitchell, A., Khetani, S.R., Shaw, G.M., Stolz, D., Yamane, D., Lemon, S.M., Gale, M., Shah, V., and Rosen, H.R. Hepatitis C virus infection induces autocrine interferon signaling by human liver endothelial cell and release of exosomes, which inhibits viral replication. Gastroenterology 148(2):392-402.e13 [Epub ahead of print] (2014)
17. Schwartz, R.E., Fleming, H.E., Khetani, S.R., and Bhatia, S.N. Pluripotent stem cell-derived hepatocyte-like cells. Biotechnology Advances 32(2):504-513 (2014)
2013
16. Chan, T.S., Yu, H., Moore, A., Khetani, S.R. and Tweedie, D. Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac. Drug Metabolism and Disposition 41(12):2024-1032 (2013)
15. Ukairo, O., McVay, M., Krzyzewski, S., Aoyama, S., Rose, K., Andersen, M.E., Khetani, S.R., and LeCluyse, E.L. Bioactivation and toxicity of acetaminophen in a rat hepatocyte micropatterned co-culture system. Journal of Biochemical and Molecular Toxicology 27(10):471-480 (2013)
14. Ukairo, O., Kanchagar, C., Moore, A., Shi, J., Gaffney, J., Aoyama, S., Rose, K., Krzyzewski, S., McGeehan, J., Andersen, M.E., Khetani, S.R., and LeCluyse, E.L. Long-term stability of primary rat hepatocytes in micropatterned co-cultures. Journal of Biochemical and Molecular Toxicology 27(3):204-212 (2013)
13. Khetani, S.R., Kanchagar, C., Krzyzewski, S., Aleo, M., and Will, Y. Use of micropatterned co-cultures to detect compounds that cause drug induced liver injury in humans. Toxicological Sciences 132(1):107-117 (2013)
2004 - 2012
12. Wang, W.W., Khetani, S.R., Krzyzewski, S., Duignan, D.B., and Obach, R.S. Assessment of a micropatterned hepatocyte coculture system to generate major human excretory and circulating drug metabolites. Drug Metabolism and Disposition 38(10):1900-1905 (2010)
11. Ploss, A.*, Khetani, S.R.*, Jones, C.T., Syder, A. J., Trehan, K., Gaysinskaya, V.A., Mu, K., Ritola, K. D., Rice, C.M., and Bhatia, S.N. Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures. Proceedings of the National Academy of Sciences 107(7):3141-3145 (2010) *These authors contributed equally to this work
10. Jones, C.T., Catanes, M.T., Law, L.M., Khetani, S.R., Syder A.J., Ploss, A., Oh, T.S., Schoggins, J.W., MacDonald, M.R., Bhatia S.N., Rice, C.M. Real-time imaging of hepatitis C virus infection using a fluorescent cell-based reporter system. Nature Biotechnology 28(2):167-171 (2010)
9. March, S., Hui, E.E., Underhill G.H., Khetani, S., and Bhatia, S.N. Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro. Hepatology 50(3):920-928 (2009)
8. Chen, A.A.*, Khetani, S.R.*, Bhatia, S.N., and Van Vliet, K. J. Modulation of hepatocyte phenotype in vitro via chemomechanical tuning of polyelectrolyte multilayers. Biomaterials 30(6):1113-1120 (2009) *These authors contributed equally to this work
7. Khetani, S.R., Chen, A.A., Ranscht, B., and Bhatia, S.N. T-cadherin modulates hepatocyte functions in vitro. FASEB Journal 22(11):3768-75 (2008)
6. Khetani, S.R., and Bhatia, S.N. Microscale human liver tissue for drug development. Nature Biotechnology 26(1):120-126 (2007)
5. Allen, J.W., Khetani, S.R., Johnson, R.S., and Bhatia, S.N. In vitro liver tissue model established from transgenic mice: role of HIF-1alpha on hypoxic gene expression. Tissue Engineering 12(11):3135-3147 (2006)
4. Khetani, S.R., and Bhatia, S.N. Engineering tissues for in vitro applications. Current Opinion in Biotechnology 17(5):524-531 (2006)
3. Chen, A.A*., Derfus, A.M*., Khetani, S.R., and Bhatia, S.N. Quantum dots to monitor siRNA delivery and improve gene silencing. Nucleic Acids Research 33(22):190 (2005) *These authors contributed equally
2. Khetani, S.R., Szulgit, G., Del Rio, J.A., Barlow, C., and Bhatia, S.N. Exploring interactions between rat hepatocytes and nonparenchymal cells using gene expression profiling. Hepatology 40(3):545-554 (2004)
1. Allen, J.W., Khetani, S.R., and Bhatia, S.N. In vitro zonation and toxicity in a hepatocyte bioreactor. Toxicological Sciences 84:110-119 (2004)
BOOK CHAPTERS
5. Monckton, C.P. and Khetani, S.R. "Engineered Human Liver Co-cultures for Investigating Drug-Induced Liver Injury", Chapter 11 in Drug Induced Liver Toxicity, First Edition, doi: 10.1007/978-1-4939-7677-5. M. Chen and Y. Will (editors), Springer (2018)
4. Ware, B.R. and Khetani, S.R. "Micropatterned Co-Cultures of Induced Pluripotent Stem Cell-Derived Hepatocytes and Stromal Cells for Prediction of Drug-Induced Liver Injury", Chapter 16 in Stem Cell-Derived Models in Toxicology, First Edition, doi: 10.1007/978-1-4939-6661-5. M. Clements and L. Roquemore (editors), Springer, p. 311-334 (2016)
3.
Hui, E.E, Khetani, S.R., and Bhatia, S.N. "Micromechanical control of cell-cell interactions", Chapter 3 in Microdevices in Biology and Medicine, First Edition, ISBN-10: 1596934042. Y. Nahmias and S. N. Bhatia (editors), Artech House, p. 43-63 (2009)
2. Underhill, G.H., Khetani, S.R., Chen, A.A., and Bhatia, S.N. "Liver", Chapter 48 in Principles of Tissue Engineering, Third Edition, ISBN-10: 0123706157. R. Lanza, R. Langer, and J.P. Vacanti (editors), Elsevier, p. 707-732 (2007)
1. Underhill, G.H., Felix, J., Allen, J.W., Tsang, V.L., Khetani, S.R., and Bhatia, S.N. "Tissue engineering of the liver", Chapter 15 in Culture of Cells for Tissue Engineering. First Edition, ISBN-10: 0471629359. G. Vunjak-Novakovic and R.I. Freshney (editors), John Wiley and Sons, p. 417-473 (2006)
