Human microphysiological systems for drug development

Science ◽  
2021 ◽  
Vol 373 (6561) ◽  
pp. 1304-1306
Author(s):  
Adrian Roth ◽  
Keyword(s):  
Drug Development ◽  
Microphysiological Systems

scholarly journals Human-on-a-chip design strategies and principles for physiologically based pharmacokinetics/pharmacodynamics modeling

2015 ◽  
Vol 7 (4) ◽  
pp. 383-391 ◽  
Author(s):  
Hasan Erbil Abaci ◽  
Michael L. Shuler
Keyword(s):  
Drug Development ◽  
Development Studies ◽  
Human Tissues ◽  
Design Strategies ◽  
Physiologically Based Pharmacokinetics ◽  
Microfluidic Platforms ◽  
Chip Design ◽  
Microphysiological Systems ◽  
Physiologically Based

Advances in maintaining multiple human tissues on microfluidic platforms has led to a growing interest in the development of microphysiological systems for drug development studies.

scholarly journals Microphysiological Systems: Stakeholder Challenges to Adoption in Drug Development

2021 ◽  
pp. 1-13
Author(s):  
Passley Hargrove-Grimes ◽  
Lucie A. Low ◽  
Danilo A. Tagle
Keyword(s):  
Human Physiology ◽  
Pharmaceutical Industry ◽  
Drug Development ◽  
End Users ◽  
Regulatory Agencies ◽  
Functional Level ◽  
Multiple Stakeholder ◽  
Widespread Adoption ◽  
Microphysiological Systems

Microphysiological systems (MPS) or tissue chips/organs-on-chips are novel <i>in vitro</i> models that emulate human physiology at the most basic functional level. In this review, we discuss various hurdles to widespread adoption of MPS technology focusing on issues from multiple stakeholder sectors, e.g., academic MPS developers, commercial suppliers of platforms, the pharmaceutical and biotechnology industries, and regulatory organizations. Broad adoption of MPS technology has thus far been limited by a gap in translation between platform developers, end-users, regulatory agencies, and the pharmaceutical industry. In this brief review, we offer a perspective on the existing barriers and how end-users may help surmount these obstacles to achieve broader adoption of MPS technology.

scholarly journals Tissue chips – innovative tools for drug development and disease modeling

Lab on a Chip ◽  
2017 ◽  
Vol 17 (18) ◽  
pp. 3026-3036 ◽  
Author(s):  
L. A. Low ◽  
D. A. Tagle
Keyword(s):  
Tissue Engineering ◽  
Drug Development ◽  
Disease Modeling ◽  
High Rate ◽  
Human Organs ◽  
Recent Advances ◽  
Microphysiological Systems ◽  
Rate Of Failure

The high rate of failure during drug development is well-known, however recent advances in tissue engineering and microfabrication have contributed to the development of microphysiological systems (MPS), or ‘organs-on-chips’ that recapitulate the function of human organs.

scholarly journals A portable and reconfigurable multi-organ platform for drug development with onboard microfluidic flow control

Lab on a Chip ◽  
2017 ◽  
Vol 17 (1) ◽  
pp. 134-144 ◽  
Author(s):  
J. R. Coppeta ◽  
M. J. Mescher ◽  
B. C. Isenberg ◽  
A. J. Spencer ◽  
E. S. Kim ◽  
...  
Keyword(s):  
Drug Development ◽  
Flow Control ◽  
High Precision ◽  
Microfluidic Flow ◽  
Microphysiological Systems ◽  
Organ Model

A microphysiological systems platform with high precision onboard flow control supports organ model crosstalk for up to 2 weeks.

scholarly journals Self-contained, low-cost Body-on-a-Chip systems for drug development

2017 ◽  
Vol 242 (17) ◽  
pp. 1701-1713 ◽  
Author(s):  
Ying I Wang ◽  
Carlota Oleaga ◽  
Christopher J Long ◽  
Mandy B Esch ◽  
Christopher W McAleer ◽  
...  
Keyword(s):  
Drug Development ◽  
Development Process ◽  
Mechanical Response ◽  
High Reliability ◽  
Low Cost ◽  
Drug Development Process ◽  
Functional Responses ◽  
Drug Candidates ◽  
Organ Systems ◽  
Microphysiological Systems

Integrated multi-organ microphysiological systems are an evolving tool for preclinical evaluation of the potential toxicity and efficacy of drug candidates. Such systems, also known as Body-on-a-Chip devices, have a great potential to increase the successful conversion of drug candidates entering clinical trials into approved drugs. Systems, to be attractive for commercial adoption, need to be inexpensive, easy to operate, and give reproducible results. Further, the ability to measure functional responses, such as electrical activity, force generation, and barrier integrity of organ surrogates, enhances the ability to monitor response to drugs. The ability to operate a system for significant periods of time (up to 28 d) will provide potential to estimate chronic as well as acute responses of the human body. Here we review progress towards a self-contained low-cost microphysiological system with functional measurements of physiological responses. Impact statement Multi-organ microphysiological systems are promising devices to improve the drug development process. The development of a pumpless system represents the ability to build multi-organ systems that are of low cost, high reliability, and self-contained. These features, coupled with the ability to measure electrical and mechanical response in addition to chemical or metabolic changes, provides an attractive system for incorporation into the drug development process. This will be the most complete review of the pumpless platform with recirculation yet written.

scholarly journals Integrated Isogenic Human Induced Pluripotent Stem Cell–Based Liver and Heart Microphysiological Systems Predict Unsafe Drug–Drug Interaction

2021 ◽  
Vol 12 ◽  
Author(s):  
Felipe T. Lee-Montiel ◽  
Alexander Laemmle ◽  
Verena Charwat ◽  
Laure Dumont ◽  
Caleb S. Lee ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Drug Development ◽  
Induced Pluripotent Stem Cell ◽  
Study Drug ◽  
Cytochrome P450 Enzyme ◽  
Human Organ ◽  
Microphysiological Systems ◽  
Drug Drug Interaction ◽  
Induced Pluripotent

Three-dimensional (3D) microphysiological systems (MPSs) mimicking human organ function in vitro are an emerging alternative to conventional monolayer cell culture and animal models for drug development. Human induced pluripotent stem cells (hiPSCs) have the potential to capture the diversity of human genetics and provide an unlimited supply of cells. Combining hiPSCs with microfluidics technology in MPSs offers new perspectives for drug development. Here, the integration of a newly developed liver MPS with a cardiac MPS—both created with the same hiPSC line—to study drug–drug interaction (DDI) is reported. As a prominent example of clinically relevant DDI, the interaction of the arrhythmogenic gastroprokinetic cisapride with the fungicide ketoconazole was investigated. As seen in patients, metabolic conversion of cisapride to non-arrhythmogenic norcisapride in the liver MPS by the cytochrome P450 enzyme CYP3A4 was inhibited by ketoconazole, leading to arrhythmia in the cardiac MPS. These results establish integration of hiPSC-based liver and cardiac MPSs to facilitate screening for DDI, and thus drug efficacy and toxicity, isogenic in the same genetic background.

scholarly journals Microphysiological systems in early stage drug development: Perspectives on current applications and future impact

2021 ◽  
Vol 46 (3) ◽  
pp. 99-114
Author(s):  
Anna K. Kopec ◽  
Ryuji Yokokawa ◽  
Nasir Khan ◽  
Ikuo Horii ◽  
James E. Finley ◽  
...  
Keyword(s):  
Drug Development ◽  
Early Stage ◽  
Microphysiological Systems

scholarly journals Multiorgan Microphysiological Systems for Drug Development: Strategies, Advances, and Challenges

2017 ◽  
Vol 7 (2) ◽  
pp. 1701000 ◽  
Author(s):  
Ying I. Wang ◽  
Carlos Carmona ◽  
James J. Hickman ◽  
Michael L. Shuler
Keyword(s):  
Drug Development ◽  
Development Strategies ◽  
Microphysiological Systems
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