TY - JOUR
AU - Aleksander Skardal
AU - Julio Aleman
AU - Steven Forsythe
AU - Shiny Rajan
AU - Sean Murphy
AU - Mahesh Devarasetty
AU - Nima Pourhabibi Zarandi
AU - Goodwell Nzou
AU - Robert Wicks
AU - Hooman Sadri-Ardekani
AU - Colin Bishop
AU - Shay Soker
AU - Adam Hall
AU - Thomas Shupe
AU - Anthony Atala
AB - Current practices in drug development have led to therapeutic compounds being approved for widespread use in humans, only to be later withdrawn due to unanticipated toxicity. These occurrences are largely the result of erroneous data generated by in vivo and in vitro preclinical models that do not accurately recapitulate human physiology. Herein, a human primary cell- and stem cell-derived 3D organoid technology is employed to screen a panel of drugs that were recalled from market by the FDA. The platform is comprised of multiple tissue organoid types that remain viable for at least 28 days, in vitro. For many of these compounds, the 3D organoid system was able to demonstrate toxicity. Furthermore, organoids exposed to non-toxic compounds remained viable at clinically relevant doses. Additional experiments were performed on integrated multi-organoid systems containing liver, cardiac, lung, vascular, testis, colon, and brain. These integrated systems proved to maintain viability and expressed functional biomarkers, long-term. Examples are provided that demonstrate how multi-organoid ‘body-on-a-chip’ systems may be used to model the interdependent metabolism and downstream effects of drugs across multiple tissues in a single platform. Such 3D in vitro systems represent a more physiologically relevant model for drug screening and will likely reduce the cost and failure rate associated with the approval of new drugs.
BT - Biofabrication
DA - 2020-02
DO - 10.1088/1758-5090/ab6d36
IS - 2
LA - en
N2 - Current practices in drug development have led to therapeutic compounds being approved for widespread use in humans, only to be later withdrawn due to unanticipated toxicity. These occurrences are largely the result of erroneous data generated by in vivo and in vitro preclinical models that do not accurately recapitulate human physiology. Herein, a human primary cell- and stem cell-derived 3D organoid technology is employed to screen a panel of drugs that were recalled from market by the FDA. The platform is comprised of multiple tissue organoid types that remain viable for at least 28 days, in vitro. For many of these compounds, the 3D organoid system was able to demonstrate toxicity. Furthermore, organoids exposed to non-toxic compounds remained viable at clinically relevant doses. Additional experiments were performed on integrated multi-organoid systems containing liver, cardiac, lung, vascular, testis, colon, and brain. These integrated systems proved to maintain viability and expressed functional biomarkers, long-term. Examples are provided that demonstrate how multi-organoid ‘body-on-a-chip’ systems may be used to model the interdependent metabolism and downstream effects of drugs across multiple tissues in a single platform. Such 3D in vitro systems represent a more physiologically relevant model for drug screening and will likely reduce the cost and failure rate associated with the approval of new drugs.
PY - 2020
EP - 025017
T2 - Biofabrication
TI - Drug compound screening in single and integrated multi-organoid body-on-a-chip systems
UR - https://dx.doi.org/10.1088/1758-5090/ab6d36
VL - 12
Y2 - 2023-07-12
SN - 1758-5090
ER -