Biology- Inspired Microphysiological Systems to Advance Patient Benefit and Animal Welfare in Drug Development

被引：194

作者：

Marx, Uwe ^{[1
,2
]}

Akabane, Takafumi ^{[3
]}

Andersson, Tommy B. ^{[4
]}

Baker, Elizabeth ^{[5
]}

Beilmann, Mario ^{[6
]}

Beken, Sonja ^{[7
]}

Brendler-Schwaab, Susanne ^{[8
]}

Cirit, Murat ^{[9
]}

David, Rhiannon ^{[10
]}

Dehne, Eva-Maria ^{[1
]}

Durieux, Isabell ^{[1
]}

Ewart, Lorna ^{[10
]}

Fitzpatrick, Suzanne C. ^{[11
]}

Frey, Olivier ^{[12
]}

Fuchs, Florian ^{[13
]}

Griffith, Linda G. ^{[14
]}

Hamilton, Geraldine A. ^{[15
]}

Hartung, Thomas ^{[16
,23
,40
]}

Hoeng, Julia ^{[17
]}

Hogberg, Helena ^{[16
]}

Hughes, David J. ^{[18
]}

Ingber, Donald E. ^{[19
]}

Iskandar, Anita ^{[28
]}

Kanamori, Toshiyuki ^{[20
]}

Kojima, Hajime ^{[21
]}

Kuehnl, Jochen ^{[22
]}

Leist, Marcel ^{[23
]}

Li, Bo ^{[24
]}

Loskill, Peter ^{[25
,26
]}

Mendrick, Donna L. ^{[27
]}

Neumann, Thomas ^{[28
]}

Pallocca, Giorgia ^{[23
]}

Rusyn, Ivan ^{[29
]}

Smirnova, Lena ^{[16
]}

Steger-Hartmann, Thomas ^{[30
]}

Tagle, Danilo A. ^{[31
]}

Tonevitsky, Alexander ^{[32
,33
]}

Tsyb, Sergej ^{[34
]}

Trapecar, Martin ^{[14
]}

van de Water, Bob ^{[35
]}

van den Eynden-van Raaij, Janny ^{[36
]}

Vultoy, Paul ^{[37
]}

Watanabe, Kengo ^{[38
]}

Wolf, Armin ^{[12
]}

Zhou, Xiaobing ^{[24
]}

Roth, Adrian ^{[39
]}

机构：

[1] TissUse GmbH, Oudenarder Str 16, D-13347 Berlin, Germany

[2] Tech Univ Berlin, Berlin, Germany

[3] Stem Cell Evaluat Technol Res Assoc, Tokyo, Japan

[4] AstraZeneca, BioPharmaceut R&D, DMPK, Res & Early Dev Cardiovasc Renal & Metab, Gothenburg, Sweden

[5] Phys Comm Responsible Med, Washington, DC USA

[6] Boehringer Ingelheim Pharma GmbH & Co KG, Nonclin Drug Safety, Biberach, Germany

[7] Fed Agcy Med & Hlth Prod, Brussels, Belgium

[8] BfArM, Bonn, Germany

[9] Javelin Biotech Inc, Woburn, MA USA

[10] AstraZeneca, R&D, Clin Pharmacol & Safety Sci, Cambridge, England

[11] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA

[12] InSphero, Schlieren, Switzerland

[13] Novartis Inst BioMed Res Chem Biol & Therapeut, Basel, Switzerland

[14] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[15] Emulate Inc, Boston, MA USA

[16] Johns Hopkins Univ, Ctr Alternat Anim Testing, Bloomberg Sch Publ & Lealth, Baltimore, MD USA

[17] Philip Morris Int R&D, Neuchatel, Switzerland

[18] CN Bio Innovat Ltd, Welwyn Garden City, Herts, England

[19] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA

[20] Natl Inst Adv Ind Sci & Technol, Tokyo, Japan

[21] Japanese Ctr Validat Anim Methods, Tokyo, Japan

[22] Beiersdorf, Hamburg, Germany

[23] Univ Konstanz, Ctr Alternat Anim Testing Europe, Constance, Germany

[24] Natl Inst Food & Drug Control, Natl Ctr Safety Evaluat Drugs, Beijing, Peoples R China

[25] Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Stuttgart, Germany

[26] Eberhard Karls Univ Tubingen, Fac Med, Tubingen, Germany

[27] US FDA, Natl Ctr Toxicol Res, Silver Spring, MD USA

[28] Nortis Inc, Seattle, WA USA

[29] Texas A&M Univ, College Stn, TX USA

[30] Bayer, Invest Toxicol, Berlin, Germany

[31] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA

[32] Russian Acad Sci, MM Shemyakin & Yu A Ovchinnikov Inst Bioorgan Che, Moscow, Russia

[33] Natl Res Univ Higher Sch Econ, Moscow, Russia

[34] Russian Minist Prod & Trade, Moscow, Russia

[35] Leiden Univ, Leiden, Netherlands

[36] Inst Human Organ & Dis Model Technol, Eindhoven, Netherlands

[37] MIMETAS BV, Leiden, Netherlands

[38] Daiichi Sankyo Co Ltd, Tokyo, Japan

[39] F Hoffmann La Roche Ltd, Roche Innovat Ctr Basel, Basel, Switzerland

[40] AxoSim Inc, New Orleans, LA USA

来源：

ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION | 2020年 / 37卷 / 03期

关键词：

D O I：

10.14573/altex.2001241

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The first microfluidic microphysiological systems (MPS) entered the academic scene more than 15 years ago and were considered an enabling technology to human in vitro (patho)biology and, therefore, to provide alternative approaches to laboratory animals in pharmaceutical drug development and academic research. Currently, the field generates more than a thousand scientific publications per year. Despite the MPS hype in academia and by platform providers, which say this technology is about to reshape the entire in vitro culture landscape in basic and applied research, MPS approaches neither have been widely adopted by the pharmaceutical industry yet nor have they reached regulated drug authorization processes. Here, 46 leading international experts from all stakeholder groups - academia, MPS supplier industry, pharmaceutical and consumer products industries, and leading regulatory agencies - analyzed challenges and hurdles along the MPS-based assay life cycle in the second workshop of its kind in June 2019. The main findings were that the level of qualification of MPS-based assays for a given context of use and communication gaps between stakeholders are the major challenges slowing industrial adoption by end users, which in turn is causing a regulatory acceptance dilemma. This report elaborates on these findings and proposes solutions by providing recommendations and a roadmap towards regulatory acceptance of MPS-based models, which will benefit patients and further reduce laboratory animal use in drug development. Finally, the potential of MPS-based human disease models to feed back into laboratory animal replacement in basic life science research is discussed.

引用

页码：365 / 394

页数：30

共 90 条

[1] Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform [J].

Achberger, Kevin ;

Probst, Christopher ;

Haderspeck, Jasmin ;

Bolz, Sylvia ;

Rogal, Julia ;

Chuchuy, Johanna ;

Nikolova, Marina ;

Cora, Virginia ;

Antkowiak, Lena ;

Haq, Wadood ;

Shen, Nian ;

Schenke-Layland, Katja ;

Ueffing, Marius ;

Liebau, Stefan ;

Loskill, Peter .

ELIFE, 2019, 8

[2] Microphysiological lung models to evaluate the safety of new pharmaceutical modalities: a biopharmaceutical perspective [J].

Ainslie, Garrett R. ;

Davis, Myrtle ;

Ewart, Lorna ;

Lieberman, Linda A. ;

Rowlands, David J. ;

Thorley, Andrew J. ;

Yoder, Gorm ;

Ryan, Anne M. .

LAB ON A CHIP, 2019, 19 (19) :3152-3161

[3]

[Anonymous], 2009, Official Journal of the European Union

[4] A Tissue Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome Using Human iPSC-derived Smooth Muscle Cells [J].

Atchison, Leigh ;

Zhang, Haoyue ;

Cao, Kan ;

Truskey, George A. .

SCIENTIFIC REPORTS, 2017, 7

[5] A LIVING SYSTEM ON A CHIP [J].

Baker, Monya .

NATURE, 2011, 471 (7340) :661-665

[6]

BALLS M, 1990, ATLA-ALTERN LAB ANIM, V18, P313

[7] Organ-on-Chip Recapitulates Thrombosis Induced by an anti-CD154 Monoclonal Antibody: Translational Potential of Advanced Microengineered Systems [J].

Barrile, Riccardo ;

van der Meer, Andries D. ;

Park, Hyoungshin ;

Fraser, Jacob P. ;

Simic, Damir ;

Teng, Fang ;

Conegliano, David ;

Justin Nguyen ;

Jain, Abhishek ;

Zhou, Mimi ;

Karalis, Katia ;

Ingber, Donald E. ;

Hamilton, Geraldine A. ;

Otieno, Monicah A. .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2018, 104 (06) :1240-1248

[8] Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model [J].

Bauer, Sophie ;

Huldt, Charlotte Wennberg ;

Kanebratt, Kajsa P. ;

Durieux, Isabell ;

Gunne, Daniela ;

Andersson, Shalini ;

Ewart, Lorna ;

Haynes, William G. ;

Maschmeyer, Ilka ;

Winter, Annika ;

Ammala, Carina ;

Marx, Uwe ;

Andersson, Tommy B. .

SCIENTIFIC REPORTS, 2017, 7

[9] Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery [J].

Beaurivage, Claudia ;

Naumovska, Elena ;

Chang, Yee Xiang ;

Elstak, Edo D. ;

Nicolas, Arnaud ;

Wouters, Heidi ;

van Moolenbroek, Guido ;

Lanz, Henriette L. ;

Trietsch, Sebastiaan J. ;

Joore, Jos ;

Vulto, Paul ;

Janssen, Richard A. J. ;

Erdmann, Kai S. ;

Stallen, Jan ;

Kurek, Dorota .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (22)

[10] Optimizing Drug Discovery by Investigative Toxicology: Current and Future Trends [J].

Beilmann, Mario ;

Boonen, Harrie ;

Czich, Andreas ;

Dear, Gordon ;

Hewitt, Philip ;

Mow, Limas ;

Newham, Peter ;

Oinonen, Tea ;

Pognan, Francois ;

Roth, Adrian ;

Valentin, Jean-Pierre ;

Van Goethem, Freddy ;

Weaver, Richard J. ;

Birk, Barbara ;

Boyer, Scott ;

Caloni, Francesca ;

Chen, Alice E. ;

Corvi, Raffaella ;

Cronin, Mark T. D. ;

Daneshian, Manias ;

Ewart, Lorna C. ;

FitzGerald, Rex E. ;

Hamilton, Geraldine A. ;

Hartung, Thomas ;

Kangas, Joshua D. ;

Kramer, Nynke L. ;

Leist, Marcel ;

Marx, Uwe ;

Polak, Sebastian ;

Rovida, Costanza ;

Testai, Emanuela ;

van de Water, Bob ;

Vulto, Paul ;

Steger-Hartmann, Thomas .

ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION, 2019, 36 (02) :289-313

← 1 2 3 4 5 6 7 8 9 →