Scientific Publications & Presentations | InSphero

Organ-on-a-chip Solutions

Boos, JA, Misun, PM, Michlmayr, A, Hierlemann, A, Frey, O (2019)  Microfluidic Multitissue Platform for Advanced Embryotoxicity Testing In Vitro Adv. Sci. 2019, 1900294. https://doi.org/10.1002/advs.201900294

Lohasz, C, Frey, O, Bonanini, F, Renggli, K, Hierlemann, A (2019) Tubing-free microfluidic microtissue culture system featuring gradual, in vivo-like substance exposure profiles Front. Bioeng. Biotechnol., 02 April 2019 | https://doi.org/10.3389/fbioe.2019.00072

Lohasz C, Rousset N, Renggli K, Hierlemann A, Frey O (2019)  Scalable Microfluidic Platform for Flexible Configuration of and Experiments with Microtissue Multiorgan Models SLAS Technol 2019 Feb;24(1):79-95. doi: 10.1177/2472630318802582. Epub 2018 Oct 5.

Aeby E, Misun PM, Hierlemann A, Frey, O (2018)  Microfluidic Hydrogel Hanging‐Drop Network for Long‐Term Culturing of 3D Microtissues and Simultaneous High‐Resolution Imaging. Adv. Biosys. 2018, 2, 1800054. doi: https://doi.org/10.1002/adbi.201800054.

Schmid, YRF, Bürgel, SC, Misun, PM, Hierlemann, A, Frey, O (2016) Electrical impedance spectroscopy for microtissue spheroid analysis in hanging-drop networks. ACS Sens.2016181028-1035; 2016, July 18; doi.org/10.1021/acssensors.6b00272

Misun PM, Rothe J, Schmid YRF, Hierlemann A, Frey O. (2016) Multi-analyte biosensor interface for real-time monitoring of 3D microtissue spheroids in hanging-drop networks. Microsyst Nanoeng. 2016 Jun 6;2:16022. doi: 10.1038/micronano.2016.22.

Bürgel, SC, Diener, L, Frey, O, Kim, J-Y, Hierlemann, A (2016)  Automated, multiplexed electrical impedance spectroscopy platform for continuous monitoring of microtissue spheroids. Anal. Chem.2016882210876-10883; 2016 Sept 21; doi.org/10.1021/acs.analchem.6b01410

Rismani Yazdi S, Shadmani A, Bürgel SC, Misun PM, Hierlemann A, Frey O (2015)  Adding the “heart” to hanging drop networks for microphysiological multi-tissue experiments. Lab Chip. 2015 Nov 7;15(21):4138-47. doi: 10.1039/c5lc01000d.

Kim J, Fluri DA, Marchan R, Boonen K, Mohanty S, Singh P, Hammad S, Landuyt B, Hengstler JG, Kelm JM, Hierlemann A, and Frey O (2015) 3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis. J Biotechnol. Jan 12. pii: S0168-1656(15)00012-7. doi: 10.1016/j.jbiotec.2015.01.003.

Kim J, Fluri DA, Kelm JM, Hierlemann A, and Frey O (2014) 96-well format microfluidic platform for parallel interconnection of multiple multicellular spheroids. J Lab Autom. 2015 Jun;20(3):274-82. doi: 10.1177/2211068214564056

Frey O, Misun PM, Fluri DA, Hengstler JG and Hierlemann A (2014) Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nat Commun. Jun 30; 5:4250. doi: 10.1038/ncomms5250.

NASH and NAFLD

Hall KC, Bernier SG, Jacobson S, Liu G, Zhang PY, Sarno R, Catanzano V, Currie MG, Masferrer JL (2019) sGC stimulator praliciguat suppresses stellate cell fibrotic transformation and inhibits fibrosis and inflammation in models of NASH. PNAS May 2019, 116 (22) 11057-11062; DOI: 10.1073/pnas.1821045116.

Mukherjee S, Zheinin L, Sanfiz A, Pan J, Li Z, Yarde M, McCarty J, Jarai G (2019) Development and validation of an in vitro 3D model of NASH with severe fibrotic phenotype. Am J Transl Res. 2019 Mar 15; 11(3):1531-1540.

Guye P, Thoma E, Frey O (2019) Considerations for engineering composable, disease-tunable 3D human microtissues for drug discovery. Drug Discovery World  Winter 2018/19:45-50.

Diabetes and Islet Biology

Lorza-Gil E, Gerst F, Barroso Oquendo M, Deschl U, Häring H, Beilmann M, Ullrich S (2019) Glucose, Adrenaline and Palmitate antagonistically regulate insulin and glucagon secretion in human pseuodislets. Sci Rep July 16;9:10261. doi: 10.1038/s41598-019-46545-6.

Bakhti M, Böttcher A, Lickert H (2019) Modelling the endocrine pancreas in health and disease. Nat Rev Endocrinol. 2019 Mar;15(3):155-171. doi: 10.1038/s41574-018-0132-z

Ämmälä C, Drury WJ, Knerr L, Ahlstedt I, Stillemark-Billton P, Wennberg-Huldt C, Andersson EM, Valeur E, Jansson-Löfmark R, Janzén D, Sundström L, Meuller J, Claesson J, Andersson P, Johansson C, Lee RG, Prakash TP, Seth PP, Monia BP and Andersson S (2018) Targeted delivery of antisense oligonucleotides to pancreatic β-cells Science Advances 17 Oct 2018: Vol. 4, no. 10, eaat3386 DOI: 10.1126/sciadv.aat3386

Bauer S, Wennberg Huldt C, Kanebratt KP, Durieux I, Gunne D, Andersson S, Ewart L, Haynes WG, Maschmeyer I, Winter A, Ämmälä C, Marx U, Andersson TB (2017) Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model. Sci Rep. Nov 6;7(1):14620. doi: 10.1038/s41598-017-14815-w.

Li G, Wu B, Ward MG, Chong ACN, Mukherjee S, Chen S, Hao M (2016) Multifunctional in vivo imaging of pancreatic islets during diabetes development.  Aug 1; 143(15):e1.2. doi: 10.1242/dev.142372

Bader E, Migliorini A, Gegg M, Moruzzi N, Gerdes J, Roscioni SS, Bakhti M, Brandl E, Irmler M, Beckers J, Aichler M, Feuchtinger A, Leitzinger C, Zischka H, Wang-Sattler R, Jastroch M, Tschöp M, Machicao F, Staiger H, Häring HU, Chmelova H, Chouinard JA, Oskolkov N, Korsgren O, Speier S, Lickert H  Identification of proliferative and mature ß-cells in the islets of Langerhans. Nature. 2016 Jul 21;535(7612):430-4. DOI: 10.1038/nature18624

Zuellig RA, Cavallari G, Gerber P, Tschopp O, Spinas GA, Moritz W, Lehmann R (2014) Improved physiological properties of gravity-enforced reassembled rat and human pancreatic pseudo-islets. J Tissue Eng Regen Med. Apr 16. doi: 10.1002/term.1891.

Oncology

Willis, RC. (2018). Special Report on Cancer: Aiming for Avatars. Drug Discovery News. June 2019, Vol 15 No 6.

 

Herter S, Morra L, Schlenker R, Sulcova J, Fahrni L, Waldhauer I, Lehmann S, Reislander T, Agarkova I, Kelm JM, Klein C, Umana P, Bacac M. (2017). A novel three-dimensional heterotypic spheroid model for the assessment of the activity of cancer immunotherapy agents. Cancer Immunol Immunother. Jan; 66(1):129-140. doi: 10.1007/s00262-016-1927-1. Epub 2016 Nov 17.

Huber JM, Amann A, Koeck S, Lorenz E, Kelm JM, Obexer P, Zwierzina H, Gamerith G (2016) Evaluation of assays for drug efficacy in a three-dimensional model of the lung. J Cancer Res and Clin Oncol. Sep;142(9):1955-66. doi 10.1007/s00432-016-2198-0. epub 2016 Jul 16.

Falkenberg, N., Höfig I, Rosemann M., Szumielewski J., Richter S., Schorpp K., Hadian K., Aubele M., Atkinson M.J., Anastasov N. (2016). Three-dimensional microtissues essentially contribute to preclinical validations of therapeutic targets in breast cancer. Cancer Med. 2016 Jan 14. doi: 10.1002/cam4.630. [Epub ahead of print]

Anastasov N., Hofig I., Radulovic V., Strobel S., Salomon M., Lichtenberg J., Rothenaigner I., Hadian K., Kelm J.M., Thirion C., Atkinson M.J. (2015). A 3D-microtissue-based phenotypic screening of radiation resistant tumor cells with synchronized chemotherapeutic treatment. BMC Cancer. Jun 10. 15:466. doi: 10.1186/s12885-015-1481-9.

Falkenberg N., Anastasov N., Hofig I, Bashkueva K., Hofler H., Rosemann M., Aubele M. (2015). Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression in vivo. Mol Oncol. Jan 9 (1): 282-94. doi: 10.1016/j.molonc.2014.08.012. Epub 2014 Sep 6.

Amann A., Zwierzina M., Gamerith G., Bitsche M., Huber J.M., Vogel G.F., Blumer M., Koeck S., Pechriggl E.J., Kelm J.M., Hilbe W. and Zwierzina H. (2014). Development of an innovative 3D cell culture system to study tumour–stroma interactions in non-small cell lung cancer cells. PLoS One.

Thoma C., Zimmermann M., Agarkova I., Kelm J.M. and Krek W. (2014). 3D cell culture systems modeling tumor growth determinants in cancer target discovery. Adv Drug Deliv Rev.

Thoma C., Stroebel S., Rösch N., Calpe B., Krek W. and Kelm J.M. (2013). A High-Throughput–Compatible 3D Microtissue Co-culture System for Phenotypic RNAi Screening Applications. Journal of Biomolecular Screening.

Oberdanner C., Kopish K., Stevenson J., Salomon M., Drewitz M. and Kelm J.M. (2012). Multiplexed Drug Assessment in 3D. Combining Luminescence and Fluorescence Genetic Reporters to Assess Drug Effects. Genetic Engineering & Biotechnology News.

Helbling M.M., Drewitz M., Bieri M., Lotz C., Wyder L., Lehembre F., Moritz W., Lichtenberg J., Regenass U. and Kelm J.M. (2011). Characterization and Drug Sensitivity Testing of HTS-Compatible Cancer Microtissues. American Association of Cancer Research Annual Meeting, Orlando.

Kelm, J.M., Timmins N.E., Brown C.J., Fussenegger M. and Nielsen L.K. (2003). Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types. Biotechnol Bioeng 83, 173-80.

Liver Toxicology

Wardwell, J, Kostadinova, R, Wolf, A (2019) Translational Safety:  The Next Frontier for 3D In Vitro Liver Toxicity Testing. European Biopharma Review, Summer 2019, p 64-69.

Kermanizadeh A, Brown DM, Moritz W, Stone V (2019) The importance of inter-individual Kupffer cell variability in the governance of hepatic toxicity in a 3D primary human liver microtissue model Scientific reports, 9(1), 7295. doi:10.1038/s41598-019-43870-8.

Messner S, Fredriksson L, Lauschke VM, Roessger K, Escher C, Bober M, Kelm JM, Ingelman-Sundberg M, Moritz W.  (2017) Transcriptomic, Proteomic, and Functional Long-term Characterization of Multicellular Three-Dimensional Human Liver Microtissues. Applied In Vitro Toxicology. doi: 10.1089/aivt.2017.0022.

Proctor WR, Foster AJ, Vogt J, Summers C, Middleton B, Pillings MA, Shienson D, Kijanska M, Stroebel S, Kelm JM, Morgan P, Messner S, Williams D.  (2017) Utility of spherical human liver microtissues for prediction of clinical drug-induced liver injury. Arch Toxicol. Aug;91(8):2849-2863. doi: 10.1007/s00204-017-2002-1.

F. Paech, S. Messner, J. Spickermann, M. Wind, A.-H. Schmitt-Hoffmann, A.T. Witschi, B.A. Howell, R.J. Church, J. Woodhead, M. Engelhardt, S. Krähenbühl, M. Maurer (2017) Mechanisms of hepatotoxicity associated with the monocyclic β-lactam antibiotic BAL30072. Arch. Toxicol. doi:10.1007/s00204-017-1994-x..

Hendriks DF, Fredriksson Puigvert L, Messner S, Mortiz W, Ingelman-Sundberg M (2016) Hepatic 3D spheroid models for the detection and study of compounds with cholestatic liability. Sci Rep. 2016 Oct 19;6:35434. doi: 10.1038/srep35434.

Linfeng L, Zhou Q, Voss TC, Quick KL, LaBarbera DV (2016) High-throughput imaging: Focusing in on drug discovery in 3D. Methods. 2016 Mar 1;96:97-102. doi: 10.1016/j.ymeth.2015.11.013.

Bruderer R, Bernhardt OM, Gandhi T, Miladinovic SM, Cheng LY, Messner S, Ehrenberger T, Zanotelli V, Butscheid Y, Escher C, Vitek O, Rinner O, and Reiter L (2015) Extending the limits of quantitative proteome profiling with data-independent acquisition and application to acetaminophen treated 3D liver microtissues. Mol Cell Proteomics. May;14(5):1400-10. doi: 10.1074/mcp.M114.044305.

Kermanizadeh A, Lohr M, Roursqaard M, Messner S, Gunness P, Kelm JM, Moller P, Ston V, Loft S (2014) Hepatic toxicology following single and multiple exposure of nanomaterials utilising a novel primary human 3D liver microtissue model.  Part Fibre Toxicol. Oct 20;11:56. doi: 10.1186/s12989-014-0056-2.

Fruhwurth S, Kovacs WJ, Bittman R, Messner S, Rohrl C, Stangl H (2014) Differential basolateral-apical distribution of scavenger receptor, class B, type I in cultured cells and the liver. Histochem Cell Biol. Dec;142(6):645-55. doi: 10.1007/s00418-014-1251-9.

Alepee N, Bahinski T, Daneshian M, et. al. (2014) State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology. ALTEX. Jul 14. doi: http://dx.doi.org/10.14573/altex1406111.

Kratschmar DV, Messner S, Moritz W and Odermatt A (2013) Characterization of a Rat Multi-Cell Type 3D-Liver Microtissue System. J Tissue Sci Eng 4: 130.

Merx V (2013) Cell culture: A better brew. Nature International Weekly Journal of Science. 496, 253–258.

Messner S, Agarkova I, Moritz W, and Kelm JM (2013) Multi-cell type human liver microtissues for hepatotoxicity testing. Arch. Toxicol. 87 209–13. doi:10.1007/s00204-012-0968-2.

3D Cell Technologies

Muoth C, Wichser A, Monopoli M, Correia M, Ehrlich N, Loeschner K, Gallud A, Kucki M, Diener L, Manser P, Jochum W, Wick P, Buerki-Thurnherr T (2016). A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment. Nanoscale. 2016 Oct 6;8(39):17322-17332. doi: 10.1039/c6nr06749b

Huber JM, Amann A, Koeck S, Lorenz E, Kelm JM, Obexer P, Zwierzina H, Gamerith G (2016) Evaluation of assays for drug efficacy in a three-dimensional model of the lung. J Cancer Res and Clin Oncol. 2016 Sep;142(9):1955-66. doi 10.1007/s00432-016-2198-0.

Falkenberg, N., Höfig I, Rosemann M., Szumielewski J., Richter S., Schorpp K., Hadian K., Aubele M., Atkinson M.J., Anastasov N. (2016). Three-dimensional microtissues essentially contribute to preclinical validations of therapeutic targets in breast cancer. Cancer Med. 2016 Jan 14. doi: 10.1002/cam4.630.

Keller L., Wagner Q., Offner D., Eap S., Musset A.-M., Arruebo M., Kelm J.M., Schwinté P., Benkirane-Jessel N. (2015). Integrating Microtissues in Nanofiber Scaffolds for Regenerative Nanomedicine. Materials 8, 6863-6867. add doi:10.3390/ma8105342

Anastasov N., Hofig I., Radulovic V., Strobel S., Salomon M., Lichtenberg J., Rothenaigner I., Hadian K., Kelm J.M., Thirion C., Atkinson M.J. (2015). A 3D-microtissue-based phenotypic screening of radiation resistant tumor cells with synchronized chemotherapeutic treatment. BMC Cancer. Jun 10. 15:466. doi: 10.1186/s12885-015-1481-9.

Falkenberg N., Anastasov N., Hofig I, Bashkueva K., Hofler H., Rosemann M., Aubele M. (2015). Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression in vivo. Mol Oncol. Jan 9 (1): 282-94. doi: 10.1016/j.molonc.2014.08.012.

Rimann M., Laternser S., Gvozdenovic A., Muff R., Fuchs B., Kelm J.M., Graf-Hausner U. (2014). An in vitro osteosarcoma 3D microtissue model for drug development. J Biotechnol. Sep 16; 189C:129-135. doid: 10.1016/j.jbiotec.2014.09.005.

Amann A., Zwierzina M., Gamerith G., Bitsche M., Huber J.M., Vogel G.F., Blumer M., Koeck S., Pechriggl E.J., Kelm J.M., Hilbe W. and Zwierzina H. (2014). Development of an innovative 3D cell culture system to study tumour–stroma interactions in non-small cell lung cancer cells. PLoS One. 2014 Mar 24;9(3):e92511. doi: 10.1371/journal.pone.0092511

Thoma C., Zimmermann M., Agarkova I., Kelm J.M. and Krek W. (2014). 3D cell culture systems modeling tumor growth determinants in cancer target discovery. Adv Drug Deliv Rev. 2014 Apr;69-70:29-41. doi: 10.1016/j.addr.2014.03.001

Thoma C., Stroebel S., Rösch N., Calpe B., Krek W. and Kelm J.M. (2013). A High-Throughput–Compatible 3D Microtissue Co-culture System for Phenotypic RNAi Screening Applications. J Biomol Screen. 2013 Dec;18(10):1330-7. doi: 10.1177/1087057113499071

Merx V. (2013). “Cell culture: A better brew” Nature International Weekly Jounral of Science. 496, 253–258. doi:10.1038/496253a

Kelm J.M. and Lichtenberg J.(2013). 3D Cell Culture for Compound De-Risking Innovations in Pharmaceutical Technology, Zurich.

Kelm J.M. and Fussenegger M. (2004). Microscale tissue engineering using gravity-enforced cell assembly. Trends Biotechnol. 22, 195-202.

Kelm J.M., Lorber V., Snedeker J.G., Schmidt D., Broggini-Tenzer A., Weisstanner M., Odermatt B., Mol A., Zünd G. and Hoerstrup S.P. (2010). A Novel Concept for Scaffold-Free Vessel Tissue Engineering: Self-Assembly of Microtissue Building Blocks J Biotech 148, 46-55.

Kelm J.M. and Fussenegger M. (2010) Scaffold-free cell delivery for use in regenerative medicine Adv Drug Delivery Rev 62, 753-64.

Diaz Sanchez-Bustamante C., Kelm J.M., Mitta B. and Fussenegger M. (2006). Heterologous Protein Production Capacity of Mammalian Cells in 2D and 3D cultures. Biotechnol Bioeng. 93, 169-180.

Cardiac and Stem Cell-Derived Microtissues

Beauchamp P, Moritz W, Kelm JM, Ullrich ND, Agarkova I, Anson BD, Suter TM, Zuppinger C (2015) Development and Characterization of a Scaffold-Free 3D Spheroid Model of Induced Pluripotent Stem Cell Derived Human Cardiomyocytes. Tissue Eng Part C Methods. 2015 Aug;21(8):852-61. doi: 10.1089/ten.TEC.2014.0376.

Rismani Yazdi S, Shadmani A, Bürgel SC, Misun PM, Hierlemann A, Frey O (2015)  Adding the “heart” to hanging drop networks for microphysiological multi-tissue experiments. Lab Chip. 2015 Nov 7;15(21):4138-47. doi: 10.1039/c5lc01000d.

Suter-Dick L, Alves PM, Blaauboer BJ, Bremm KD, Brito C, Coecke S, Flick B, Fowler P, Hescheler J, Ingelman-Sundberg M, Jennings P, Kelm JM, Manou I, Mistry P, Moretto A, Roth A, Stedman D, van de Water B, Beilmann M (2015) Stem cell derived (SCD) systems in toxicology assessment. Stem Cells Dev. 2015 Jun 1;24(11):1284-96. doi: 10.1089/scd.2014.0540.

Kelm JM, Djonov V, Hoerstrup SP, Guenter CI, Ittner LM, Greve F, Hierlemann A, Perriard JC, Ehler E, Fussenegger M (2006)  Tissue-Transplant Fusion and Vascularization of Myocardial Micro-and Macrotissues Implanted into Chicken Embryos and Rats. Tissue Eng. 12, 2541-2553. DOI: 10.1089/ten.2006.12.2541.  Winning article of the young investigator award 2006. European Society of Artificial Organs (ESAO).

Kelm, JM, Ehler E, Nielsen LK, Schlatter S, Perriard JC and Fussenegger M (2004)  Design of Artificial Myocardial Microtissues. Tissue Eng. 10, 201-214. DOI: 10.1089/107632704322791853

Embryotoxicity Testing

Seiler AE, Spielmann H (2011) The validated embryonic stem cell test to predict embryotoxicity in vitro Nat protoc. 2011 Jun 16;6(7):961-78.doi: 10.1038/nprot.2011.348..

Regenerative Medicine and Tissue Engineering

Keller L., Wagner Q., Offner D., Eap S., Musset A.-M., Arruebo M., Kelm J.M., Schwinté P., Benkirane-Jessel N. (2015). Integrating Microtissues in Nanofiber Scaffolds for Regenerative Nanomedicine. Materials 8, 6863-6867. doi:10.3390/ma8105342.

Rimann M., Laternser S., Gvozdenovic A., Muff R., Fuchs B., Kelm J.M., Graf-Hausner U. (2014). An in vitro osteosarcoma 3D microtissue model for drug development. J Biotechnol. Sep 16; 189C:129-135. doid: 10.1016/j.jbiotec.2014.09.005.

Kelm J.M. and Fussenegger M. (2010) Scaffold-free cell delivery for use in regenerative medicine Adv Drug Delivery Rev 62, 753-64. doi: 10.1016/j.addr.2010.02.003.

Diaz Sanchez-Bustamante C., Kelm J.M., Egermann E., Djonov V. and Fussenegger M. (2007) Ectopic expression of DFosB mediates transdifferention of adipose-like spheroids into osteo-like microtissues. Tissue Eng 14, 1377-94. doi: 10.1089/ten.tea.2007.0185

Kelm J.M., Djonov V., Ittner L.M., Born W., Hoerstrup S.P. and Fussenegger M. (2006). Design of Custom-Shaped Vascularized Tissues Using Microtissue Spheroids as Minimal Building Units. Tissue Eng. 12, 2151-2160.  DOI: 10.1089/ten.2006.12.2151.

Kelm J.M., Diaz Sanchez-Bustamante C., Ehler E., Hoerstrup S.P., Djonov D., Ittner L.M. and Fussenegger M.(2005). VEGF profiling and angiogenesis in human microtissues. J. Biotechnol. 121, 86-101. DOI: 10.1016/j.jbiotec.2005.03.016.

Kelm, J.M., Kramer B.P., Gonzalez-Nicolini V., Ley B. and Fussenegger M. (2004). Synergies of Microtissue Design, Viral Transduction and Adjustable Transgene Expression for Regenerative Medicine.” Biotechnol Appl Biochem. 39, 3-16. DOI: 10.1042/BA20030124.