Peer-reviewed Papers and
Trade Magazine Articles

Experimental Program Design Considerations for Optimized Use of Preclinical Models in NASH Drug Discovery, Grepper S, Dowell K, Thoma E (2020), Genetic Engineering and Biotechnology News, January 2020

Evolving Models for NASH Drug Discovery, Grepper S, Kostadinova R, Thoma E, Wolf A (2019), Drug Discovery World  Fall 2019:61-66.

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

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

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

Effect of IL4 and IL10 on a human in vitro type 1 diabetes model, Susanne E M Pfeiffer, Estefania Quesada-Masachs, Sara McArdle, Samuel Zilberman, Burcak Yesildag, Zbigniew Mikulski, Matthias von Herrath, Clin Immunol, 2022 Aug;241:109076. doi: 10.1016/j.clim.2022.109076

Upregulation of HLA class II in pancreatic beta cells from organ donors with type 1 diabetes, E. Quesada-Masachs, S. Zilberman, S. Rajendran, T. Chu, S. McArdle, W. B Kiosses, Jae-Hyun M Lee, B. Yesildag, M. Benkahla, A. Pawlowska, M. Graef, S. Pfeiffer, Z. Mikulski, M. von Herrath, Diabetologia, 2022 Feb;65(2):387-401. doi: 10.1007/s00125-021-05619-9

HIF-1alpha inhibitor PX-478 preserves pancreatic beta cell function in diabetes., E. Ilegems, G. Bryzgalova, J. Correia, B. Yesildag, E. Berra, J. L. Ruas, T. S. Pereira, P. O. Berggren,  Sci Transl Med 14, eaba9112 (2022).

Translational assessment of a genetic engineering methodology to improve islet function for transplantation., P. van Krieken, A. Voznesenskaya, A. Dicker, Y. Xiong, J. H. Park, J. I. Lee, E. Ilegems, P. O. Berggren, EBioMedicine 45, 529-541 (2019).

A microfluidic hanging-​drop-based islet perifusion system for studying glucose-​stimulated insulin secretion from multiple individual pancreatic islets, Jin, N. Rousset, A. Hierlemann, P. Misun,  Frontiers in Bioengineering and Biotechnology 2021, Vol. 9, pp. 352, doi: 10.3389/fbioe.2021.674431

Human Islet Microtissues as an In Vitro and an In Vivo Model System for Diabetes, Mir-Coll J., Moede T., Paschen M., Neelakandhan A., Valladolid-Acebes I., Leibiger B., Biernath A., Ämmälä C., Leibiger I. B., Yesildag B., Berggren P.-O.,  Int. J. Mol. Sci. 2021, 22(4), 1813,  doi:10.3390/ijms22041813

In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High Resolution, Misun, P. M., Yesildag, B., Forschler, F., Neelakandhan, A., Rousset, N., Biernath, A., Hierlemann, A., Frey, O.,  Adv. Biosys. 2020, 1900291, doi:10.1002/adbi.201900291

Targeted pharmacological therapy restores β-cell function for diabetes remission, Sachs S, Bastidas-Ponce A, Tritschler S, et al, (2020) Nat Metab 2, 192–209, doi:10.1038/s42255-020-0171-3

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

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

Targeted delivery of antisense oligonucleotides to pancreatic β-cells, 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) Science Advances 17 Oct 2018: Vol. 4, no. 10, eaat3386, doi: 10.1126/sciadv.aat3386

Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model, 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) Sci Rep. Nov 6;7(1):14620, doi: 10.1038/s41598-017-14815-w

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

Identification of proliferative and mature ß-cells in the islets of Langerhans,  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  Nature. 2016 Jul 21;535(7612):430-4. doi: 10.1038/nature18624

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

Tracing Clonal Dynamics Reveals that Two-and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma, Bolck HA., Corró C., Kahraman A., von Teichman A., Toussaint NC., Kuipers J., Chiovaro F., Koelzer VH., Pauli C., Moritz W., Bode PK., Rechsteiner M., Beerenwinkel N., Schraml P., Moch H. (2019),  Eur Urol Focus. 2019 Jun 29. pii: S2405-4560(19)30164-6, doi: 10.1016/j.euf.2019.06.009

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

A novel three-dimensional heterotypic spheroid model for the assessment of the activity of cancer immunotherapy agents, 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), Cancer Immunol Immunother. Jan; 66(1):129-140, Epub 2016 Nov 17, doi: 10.1007/s00262-016-1927-1

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

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

A 3D-microtissue-based phenotypic screening of radiation resistant tumor cells with synchronized chemotherapeutic treatment, 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), BMC Cancer. Jun 10. 15:466, doi: 10.1186/s12885-015-1481-9

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

Development of an innovative 3D cell culture system to study tumour–stroma interactions in non-small cell lung cancer cells, 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), PLoS One, doi: 10.1371/journal.pone.0092511

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

A High-Throughput–Compatible 3D Microtissue Co-culture System for Phenotypic RNAi Screening Applications, Thoma C., Stroebel S., Rösch N., Calpe B., Krek W. and Kelm J.M. (2013), Journal of Biomolecular Screening, doi: 10.1016/j.addr.2014.03.001

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

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

Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types, Kelm, J.M., Timmins N.E., Brown C.J., Fussenegger M. and Nielsen L.K. (2003). Biotechnol Bioeng 83, 173-80, doi: 10.1002/bit.10655

High-throughput transcriptomic analysis of human primary hepatocyte spheroids exposed to per- and polyfluoroalkyl substances (PFAS) as a platform for relative potency characterization, Rowan-Carroll et al. (2021),  Toxicological Sciences, March 27, 2021

Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations, Albrecht W et al. (2019), Archives of Toxicology, June 2019, Volume 93, Issue 6, p 1609-1637, doi:10.1007/s00204-019-02492-9

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

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

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

 Utility of spherical human liver microtissues for prediction of clinical drug-induced liver injury, 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), Arch Toxicol. Aug;91(8):2849-2863, doi: 10.1007/s00204-017-2002-1

Mechanisms of hepatotoxicity associated with the monocyclic β-lactam antibiotic BAL30072, 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), Arch. Toxicol, doi:10.1007/s00204-017-1994-x

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

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

Extending the limits of quantitative proteome profiling with data-independent acquisition and application to acetaminophen treated 3D liver microtissues, 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), Mol Cell Proteomics. May;14(5):1400-10, doi: 10.1074/mcp.M114.044305

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

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

 State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology, Alepee N, Bahinski T, Daneshian M, et al. (2014) ALTEX. Jul 14, doi: 10.14573/altex.1406111

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

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

A Framework for Optimizing High-Content Imaging of 3D Models for Drug Discovery, Wardwell-Swanson J, Suzuki M, Dowell KG, et al. (2020), SLAS Discovery, epub ahead of print, doi:10.1177/2472555220929291

A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment, 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), Nanoscale. 2016 Oct, 6;8(39):17322-17332, doi: 10.1039/c6nr06749b

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

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

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

A 3D-microtissue-based phenotypic screening of radiation resistant tumor cells with synchronized chemotherapeutic treatment, 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), BMC Cancer. Jun 10. 15:466, doi: 10.1186/s12885-015-1481-9

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

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

Development of an innovative 3D cell culture system to study tumour–stroma interactions in non-small cell lung cancer cells, 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), PLoS One. 2014 Mar 24;9(3):e92511, doi: 10.1371/journal.pone.0092511

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

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

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

Microscale tissue engineering using gravity-enforced cell assembly, Kelm J.M. and Fussenegger M. (2004). Trends Biotechnol. 22, 195-202, doi: 10.1016/j.tibtech.2004.02.002

A Novel Concept for Scaffold-Free Vessel Tissue Engineering: Self-Assembly of Microtissue Building Blocks, 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), J Biotech 148, 46-55, doi: 10.1016/j.jbiotec.2010.03.002

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

Heterologous Protein Production Capacity of Mammalian Cells in 2D and 3D cultures, Diaz Sanchez-Bustamante C., Kelm J.M., Mitta B. and Fussenegger M. (2006), Biotechnol Bioeng. 93, 169-180, doi: 10.1002/bit.20679

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

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

Stem cell derived (SCD) systems in toxicology assessment, 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 Cells Dev, 2015 Jun 1;24(11):1284-96, doi: 10.1089/scd.2014.0540

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

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

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

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

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

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

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

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

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

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