The Combination of Cell Cultured Technology and In Silico Model to Inform the Drug Development

Abstract

Human-derived in vitro models can provide high-throughput efficacy and toxicity data without a species gap in drug development. Challenges are still encountered regarding the full utilisation of massive data in clinical settings. The lack of translated methods hinders the reliable prediction of clinical outcomes. Therefore, in this study, in silico models were proposed to tackle these obstacles from in vitro to in vivo translation, and the current major cell culture methods were introduced, such as human-induced pluripotent stem cells (hiPSCs), 3D cells, organoids, and microphysiological systems (MPS). Furthermore, the role and applications of several in silico models were summarised, including the physiologically based pharmacokinetic model (PBPK), pharmacokinetic/pharmacodynamic model (PK/PD), quantitative systems pharmacology model (QSP), and virtual clinical trials. These credible translation cases will provide templates for subsequent in vitro to in vivo translation. We believe that synergising high-quality in vitro data with existing models can better guide drug development and clinical use.

Consideration of Commercially Available Hepatocytes as Cell Sources for Liver-Microphysiological Systems by Comparing Liver Characteristics

“…MPS comprise culture techniques for reconstructing the specific functions of human organs or tissues in a limited space, creating miniaturized human test systems. These have been actively developed in recent years [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. In MPS development, the choice of cell source to mount on the MPS is as important as the design of the device.…”

“…Additionally, pharmacokinetics, which must take into account the absorption, distribution, metabolism, and excretion of compounds in the body (ADME), is known to be species-dependent and extrapolation of animal data to humans is limited. In recent years, microphysiological systems (MPS) have been actively developed to shorten the test period and reduce animal experiments for drug development [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. MPS is an in vitro culture system in which culture cells in a precisely controlled environment in a microspace manufactured using MEMS (micro-electromechanical systems) technology, in order to bring out in vivo-like functions from human cells.…”

Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients

“…These computational models are based on algorithms and simulations to analyze biological data and predict outcomes starting from molecular simulations to whole-genome analyses. They are particularly useful to analyze large datasets, such as genomic sequences, and to identify patterns, mutations, gene expression changes, response to certain treatments and they can even support personalized medicine by predicting the most effective treatment strategies based on individual patients’ genetic profiles [ 196 ].…”

Translational Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Oxaliplatin and Irinotecan in Colorectal Cancer

“…However, drug exposure in tumor tissue is a time-dependent variable in vivo, which is a major barrier in in vitro to in vivo translation (IVIVT). The pharmacokinetic/pharmacodynamic (PK/PD) model is a valuable approach to establishing the relationship between drug dose, exposure, and response [ 13 , 14 ]. Through the integration of knowledge of physiology, disease processes, and pharmacology, various mathematical models have been established to optimize doses, design clinical trials, and provide efficacy evidence [ 13 , 15 ].…”