[Emulate] 장기칩 (Organ-on-a Chip) 관련 최신 논문을 소개해 드려요 (2023.09 updated)

ABSTRACT

Drug-induced liver injury (DILI) is a potentially lethal condition that heavily impacts the pharmaceutical industry, causing approximately 21% of drug withdrawals and 13% of clinical trial failures. Recent evidence suggests that the use of Liver-Chip technology in preclinical safety testing may significantly reduce DILI-related clinical trial failures and withdrawals. However, drug developers and regulators would benefit from guidance on the integration of Liver-Chip data into decision-making processes to facilitate the technology’s adoption.

ABSTRACT

Read this publication to learn how researchers built a prototype Chip-A1 Accessible Chip to address many of the challenges associated with the Organ-on-a-Chip technology, including incorporation of a tissue-specific extracellular matrix gel seeded with primary stromal cells, to reproducing the architectural complexity of tissues by micropatterning the gel, to extracting the gel for H&E staining.

ABSTRACT

Conventional preclinical models often miss drug toxicities, meaning the harm these drugs pose to humans is only realized in clinical trials or when they make it to market. This has caused the pharmaceutical industry to waste considerable time and resources developing drugs destined to fail. Organ-on-a-Chip technology has the potential improve success in drug development pipelines, as it can recapitulate organ-level pathophysiology and clinical responses; however, systematic and quantitative evaluations of Organ-Chips’ predictive value have not yet been reported. 

ABSTRACT

Species differences in brain and blood-brain barrier (BBB) biology hamper translation from findings in animal models to humans. This, in turn, impedes the development of medicines and brain diseases. Researchers from Emulate developed a human Brain-Chip that contains endothelial-like cells, pericytes, glia, and cortical neurons while maintaining BBB permeability at in vivo-relevant levels. With these features, the model is able to closely recapitulate neuroinflammation, allowing scientists to gain a mechanistic understanding of cell-cell interactions and BBB function during neuroinflammation with greater accuracy than they could with conventional models of the human brain.

ABSTRACT

New approach methodologies (NAMs), including in vitro toxicology methods such as human cells from simple cell cultures to 3D and organ-on-a-chip models of human lung, intestine, liver, and other organs, are challenging the traditional “norm” of current regulatory risk assessments. Uncertainty Factors continue to be used by regulatory agencies to account for perceived deficits in toxicology data. With the expanded use of human cell NAMs, the question “Are uncertainty factors needed when human cells are used?” becomes a key topic in the development of 21st-century regulatory risk assessment. Michael Dourson, Ph.D., the co-author of a paper detailing uncertainty factors within the US EPA, and Lorna Ewart, Ph.D., Executive Vice President, Science, Emulate, who is involved in developing organ-on-a-chip models, debated the topic

ABSTRACT

Human organ-on-a-chip (Organ-Chip) technology has the potential to disrupt preclinical drug discovery and improve success in drug development by recapitulating organ-level pathophysiology and clinical responses. The Innovation and Quality (IQ) consortium formed by multiple pharmaceutical and biotechnology companies to confront this challenge has published guidelines that define criteria for qualifying preclinical models, however, systematic and quantitative evaluation of the predictive value of Organ-Chips has not yet been reported. Here, 780 Liver-Chips were analyzed to determine their ability to predict drug-induced liver injury caused by small molecules identified as benchmarks by the IQ consortium. The Liver-Chip met the qualification guidelines across a blinded set of 27 known hepatotoxic and non-toxic drugs with a sensitivity of 80%, increasing to 87% when protein binding is corrected, and a specificity of 100%. A computational economic value analysis suggests that with this performance the Liver-Chip could generate $3 billion annually for the pharmaceutical industry due to increased R&D productivity.