Human organs-on-chips for disease modelling, drug development and personalized medicine

被引:776
作者
Ingber, Donald E. [1 ,2 ,3 ,4 ]
机构
[1] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA
[2] Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA
[3] Harvard Med Sch, Boston, MA 02115 USA
[4] Harvard John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02134 USA
关键词
A-CHIP; MICROPHYSIOLOGICAL SYSTEMS; HUMAN LIVER; ENDOTHELIAL-CELLS; PROXIMAL TUBULE; 1ST STEP; RESPONSES; GUT; NEPHROTOXICITY; ABSORPTION;
D O I
10.1038/s41576-022-00466-9
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
This Review discusses the types of single and multiple human organ-on-a-chip (organ chip) microfluidic devices and their diverse applications for disease modelling, drug development and personalized medicine, as well as the challenges that must be overcome for organ chips to reach their full potential. The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology with high fidelity. Here, I review how single and multiple human organ chip systems have been used to model complex diseases and rare genetic disorders, to study host-microbiome interactions, to recapitulate whole-body inter-organ physiology and to reproduce human clinical responses to drugs, radiation, toxins and infectious pathogens. I also address the challenges that must be overcome for organ chips to be accepted by the pharmaceutical industry and regulatory agencies, as well as discuss recent advances in the field. It is evident that the use of human organ chips instead of animal models for drug development and as living avatars for personalized medicine is ever closer to realization.
引用
收藏
页码:467 / 491
页数:25
相关论文
共 152 条
[1]  
Abudupataer M, 2021, ELIFE, V10, DOI [10.7554/eLife.69310, 10.7554/eLife.69310.sa1, 10.7554/eLife.69310.sa2]
[2]   Human stem cell-based retina on chip as new translational model for validation of AAV retinal gene therapy vectors [J].
Achberger, Kevin ;
Cipriano, Madalena ;
Duechs, Matthias J. ;
Schoen, Christian ;
Michelfelder, Stefan ;
Stierstorfer, Birgit ;
Lamla, Thorsten ;
Kauschke, Stefan G. ;
Chuchuy, Johanna ;
Roosz, Julia ;
Mesch, Lena ;
Cora, Virginia ;
Pars, Selin ;
Pashkovskaia, Natalia ;
Corti, Serena ;
Hartmann, Sophia-Marie ;
Kleger, Alexander ;
Kreuz, Sebastian ;
Maier, Udo ;
Liebau, Stefan ;
Loskill, Peter .
STEM CELL REPORTS, 2021, 16 (09) :2242-2256
[3]   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
[4]   Three-dimensional microengineered vascularised endometrium-on-a-chip [J].
Ahn, Jungho ;
Yoon, Min-Ji ;
Hong, Seon-Hwa ;
Cha, Hwijae ;
Lee, Danbi ;
Koo, Hwa Seon ;
Ko, Ji-Eun ;
Lee, Jungseub ;
Oh, Soojung ;
Li Jeon, Noo ;
Kang, Youn-Jung .
HUMAN REPRODUCTION, 2021, 36 (10) :2720-2731
[5]   A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal Permeability [J].
Apostolou, Athanasia ;
Panchakshari, Rohit A. ;
Banerjee, Antara ;
Manatakis, Dimitris, V ;
Paraskevopoulou, Maria D. ;
Luc, Raymond ;
Abu-Ali, Galeb ;
Dimitriou, Alexandra ;
Lucchesi, Carolina ;
Kulkarni, Gauri ;
Maulana, Tengku Ibrahim ;
Kasendra, Magdalena ;
Kerns, Jordan S. ;
Bleck, Bertram ;
Ewart, Lorna ;
Manolakos, Elias S. ;
Hamilton, Geraldine A. ;
Giallourakis, Cosmas ;
Karalis, Katia .
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY, 2021, 12 (05) :1719-1741
[6]   L-Cysteine capped zinc oxide nanoparticles induced cellular response on adenocarcinomic human alveolar basal epithelial cells using a conventional and organ-on-a-chip approach [J].
Arathi, A. ;
Joseph, X. ;
Akhil, V ;
Mohanan, P., V .
COLLOIDS AND SURFACES B-BIOINTERFACES, 2022, 211
[7]   A multi-organ-chip co-culture of liver and testis equivalents: a first step toward a systemic male reprotoxicity model [J].
Baert, Y. ;
Ruetschle, I ;
Cools, W. ;
Oehme, A. ;
Lorenz, A. ;
Marx, U. ;
Goossens, E. ;
Maschmeyer, I .
HUMAN REPRODUCTION, 2020, 35 (05) :1029-1044
[8]   Endothelial Thermotolerance Impairs Nanoparticle Transport in Tumors [J].
Bagley, Alexander F. ;
Scherz-Shouval, Ruth ;
Galie, Peter A. ;
Zhang, Angela Q. ;
Wyckoff, Jeffrey ;
Whitesell, Luke ;
Chen, Christopher S. ;
Lindquist, Susan ;
Bhatia, Sangeeta N. .
CANCER RESEARCH, 2015, 75 (16) :3255-3267
[9]  
Bai H., 2021, MECHANICAL CONTROL I, DOI [10.1101/2021.04.26.441498, DOI 10.1101/2021.04.26.441498]
[10]   Perspectives on the Evaluation and Adoption of Complex In Vitro Models in Drug Development: Workshop with the FDA and the Pharmaceutical Industry (IQ MPS Affiliate) [J].
Baran, Szczepan W. ;
Brown, Paul C. ;
Baudy, Andreas R. ;
Fitzpatrick, Suzanne C. ;
Frantz, Christopher ;
Fullerton, Aaron ;
Gan, Jinping ;
Hardwick, Rhiannon N. ;
Hillgren, Kathleen M. ;
Kopec, Anna K. ;
Liras, Jennifer L. ;
Mendrick, Donna L. ;
Nagao, Ryan ;
Proctor, William R. ;
Ramsden, Diane ;
Ribeiro, Alexandre J. S. ;
Stresser, David ;
Sung, Kyung E. ;
Sura, Radhakrishna ;
Tetsuka, Kazuhiro ;
Tomlinson, Lindsay ;
Van Vleet, Terry ;
Wagoner, Matthew P. ;
Wang, Qin ;
Arslan, Sevim Yildiz ;
Yoder, Gorm ;
Ekert, Jason E. .
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION, 2022, 39 (02) :297-314