摘要
In the last few decades,adverse reactions to pharmaceuticals have been evaluated using 2D in vitro models and animal models.However,with increasing computational power,and as the key drivers of cellular behavior have been identified,in silico models have emerged.These models are time-efficient and cost-effective,but the prediction of adverse reactions to unknown drugs using these models requires relevant experimental input.Accordingly,the physiome concept has emerged to bridge experimental datasets with in silico models.The brain physiome describes the systemic interactions of its components,which are organized into a multilevel hierarchy.Because of the limitations in obtaining experimental data corresponding to each physiome component from 2D in vitro models and animal models,3D in vitro brain models,including brain organoids and brain-on-a-chip,have been developed.In this review,we present the concept of the brain physiome and its hierarchical organization,including cell-and tissue-level organizations.We also summarize recently developed 3D in vitro brain models and link them with the elements of the brain physiome as a guideline for dataset collection.The connection between in vitro 3D brain models and in silico modeling will lead to the establishment of cost-effective and time-efficient in silico models for the prediction of the safety of unknown drugs.
基金
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(grant nos.2020R1A6A3A01098991 and 2020R1A6A3A01099935)
by the National Research Foundation of Korea(NRF)funded by the Korean Government(MSIT)(grant nos.2021R1A2B5B02086828,2018M3C7A1056896,and 2020M3E5D907974412)
by a grant(grant no.20172MFDS196)funded by the Ministry of Food and Drug Safety
The funder did not play any role in study design
in the collection,analysis,and interpretation of data
in the writing of the report
and in the decision to submit the article for publication.
