Advanced Human Cell Platforms for Infectious Disease Drug Discovery toward Clinical Translation

The field of infectious disease research faces persistent challenges in bridging the gap between laboratory findings and successful clinical translation. Current outbreaks and emerging threats from respiratory viruses, bacterial pathogens, and zoonotic agents underscore the pressing need for effective therapies. Yet, despite notable advances in molecular and immunological understanding, preclinical systems often fall short in predicting human outcomes, contributing to high attrition rates in drug development pipelines. Conventional cell lines typically lack physiological complexity, while animal models, limited by interspecies differences, raise both scientific and ethical questions regarding their relevance and utility.Recent years, particularly during and following the COVID-19 pandemic, have seen rapid innovation and adoption of next-generation human cell-based models. These include air-liquid interface cultures, organoids, organ-on-a-chip platforms, and induced pluripotent stem cell (iPSC)-derived systems, which more accurately mimic human tissue architecture, cellular diversity, and intricate host–pathogen interactions. Not only do these platforms enhance our basic understanding of infectious disease biology, but there is growing evidence that they better predict clinical responses to candidate interventions, inform biomarker identification, and impact early therapeutic decision-making. However, systematic integration of these models into standard drug development processes remains incomplete, and robust frameworks for their evaluation and regulatory acceptance are still evolving.This Research Topic aims to define and promote the next generation of clinically translatable human cell-based models for infectious disease research and therapeutic development. The principal objective is to spotlight platforms and strategies that address the persistent disconnect between preclinical data and clinical efficacy, enabling more reliable prediction of human responses. We seek to attract contributions that demonstrate how advanced human models can inform infectious disease mechanisms, therapeutic target validation, identification of pharmacodynamic biomarkers, and improve clinical trial planning including dose selection, regimen optimization, and endpoint definition. By fostering interdisciplinary approaches, this Research Topic will help establish translational workflows that integrate human-relevant models as pivotal decision-making tools, simultaneously advancing scientific robustness and supporting the reduction and replacement of animal use in line with current regulatory and ethical expectations.To gather further insights into the development and application of innovative human cell-based systems for infectious disease research, we welcome articles addressing the following themes:o Comparative evaluation of human-derived in vitro models versus animal or traditional cell line systems for infectious diseaseso Applications of air-liquid interface, organoids, organ-on-a-chip, iPSC-derived, and complex 3D co-culture platformso Human cell-based models in therapeutic efficacy, drug screening, and validation of new targetso Pharmacodynamic biomarker identification and integration of human models into early drug development pipelineso Methodologies for predicting clinical dose selection, optimizing dosing strategies, and informing trial endpoint definitiono Establishment of immune-competent and multi-organ platforms for modeling host–pathogen and host–microbiome interactionso Incorporation of human model data into clinical decision-making frameworks and reduction or replacement of animal useDr. Kazuhiro Ito serves as a paid consultant to RIGImmune Inc and holds equity in the company. Dr. Yuki Yamamoto is the CEO and board member of HiLung Inc. Topic editors: Kazuhiro Ito, Hsiao-Chi Chuang, Yuki Yamamoto, Jonathan Baker Source: https://www.frontiersin.org/research-topics/80626/advanced-human-cell-platforms-for-infectious-disease-drug-discovery-toward-clinical-translation