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Microengineered cell and tissue systems for drug screening and toxicology applications: Evolution of in-vitro liver
O B Usta1, W J McCarty1, S Bale1
1Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, MA 02114, USA.
Abstract:
The liver performs many key functions, the most prominent of which is serving as the metabolic hub of the body. For this reason, the liver is the focal point of many investigations aimed at understanding an organism's toxicological response to endogenous and exogenous challenges. Because so many drug failures have involved direct liver toxicity or other organ toxicity from liver generated metabolites, the pharmaceutical industry has constantly sought superior, predictive in-vitro models that can more quickly and efficiently identify problematic drug candidates before they incur major development costs, and certainly before they are released to the public. In this broad review, we present a survey and critical comparison of in-vitro liver technologies along a broad spectrum, but focus on the current renewed push to develop "organs-on-a-chip". One prominent set of conclusions from this review is that while a large body of recent work has steered the field towards an ever more comprehensive understanding of what is needed, the field remains in great need of several key advances, including establishment of standard characterization methods, enhanced technologies that mimic the in-vivo cellular environment, and better computational approaches to bridge the gap between the in-vitro and in-vivo results.
Insights
Developing better in vitro liver models is crucial for predicting drug toxicity. Current organ-on-a-chip technologies show promise but require standardization and improved in vivo mimicry for accurate toxicological response assessment.
Area of Science:
- Hepatology and Toxicology
- Biomedical Engineering
- Drug Development
Background:
- The liver is a central metabolic organ, making it critical for understanding toxicological responses to various challenges.
- Drug development frequently faces failures due to liver toxicity or toxicity from liver-generated metabolites, highlighting the need for improved predictive models.
- Current in vitro models are continuously being refined to enhance the prediction of drug-induced toxicity.
Purpose of the Study:
- To conduct a comprehensive review and critical comparison of existing in vitro liver technologies.
- To focus on the advancements and potential of organs-on-a-chip technologies in liver research.
- To identify key areas requiring further development for more accurate in vitro toxicological assessments.
Main Methods:
- A broad survey and critical comparison of diverse in vitro liver technologies.
- Specific focus on the emerging field of organs-on-a-chip for liver applications.
- Analysis of current research trends and identified limitations in the field.
Main Results:
- Significant progress has been made in understanding the requirements for advanced in vitro liver models.
- Organs-on-a-chip technologies represent a promising avenue for improved drug toxicity screening.
- The field still faces challenges in standardization, in vivo environment mimicry, and data interpretation.
Conclusions:
- While in vitro liver models have advanced, key breakthroughs are needed for reliable toxicological predictions.
- Standardization of characterization methods is essential for comparing and validating different in vitro systems.
- Enhanced technologies that better replicate the in vivo cellular environment and improved computational methods are crucial for bridging the in vitro-in vivo gap.
