Factors of bias in spheroid-based drug screening: Fabrication method, spheroid size, and cell viability
Year: 2025
Type: article
Abstract: Spheroids have emerged as powerful tools in drug screening by providing a physiologically relevant environment that more closely mimics in vivo conditions compared to 2D cultures. Despite these advantages, experimental outcomes using spheroids are often influenced by considerable variability and bias. This review explores three key factors that affect the evaluation of drug efficacy in spheroids, including fabrication method, spheroid size, and cell viability. First, it compares five commonly used spheroid fabrication platforms, outlining their principles, advantages, and limitations. Second, it examines biological contributors to spheroid size variation, such as cell proliferation, apoptosis, protein expression, and cellular differentiation, and how they affect drug response. Third, it discusses how features such as hypoxic core development and anoikis sensitivity affect cell viability and potentially distort toxicity assessments. This review presents a conceptual framework for minimizing bias and improving reproducibility in spheroid-based drug screening.
Source: Biomedicine & Pharmacotherapy
Authors: Sunghan Lee, Jiseok Lim, Bongseop Kwak
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,610
Awards: G3682102383, G4382210962, G8626891402
OpenAlex ID: W4414422616
