Application of microphysiological systems for nonclinical evaluation of cell therapies

Main Article Content

Pelin L. Candarlioglu, Louise Delsing , Lauren Gauthier, Lauren Lewis, George Papadopoulos, May Freag, Tom S. Chan, Kimberly A. Homan, Mick D. Fellows, Amy Pointon, Kyle Kojala
[show affiliations]


Microphysiological systems (MPS) are gaining broader application in the pharmaceutical industry but have primarily been leveraged in early discovery toxicology and pharmacology studies with small molecules. The adoption of MPS offers a promising avenue to reduce animal use, improve in-vitro-to-in-vivo translation of pharmacokinetics/pharmacodynamics and toxicity correlation, and provide mechanistic understanding of model species suitability. While MPS have demonstrated utility in these areas with small molecules and biologics, MPS models in cell therapy development have not been fully explored, let alone validated. Distinguishing features of MPS, including long-term viability and physiologically relevant expression of functional enzymes, receptors, and pharmacological targets make them attractive tools for nonclinical characterization. However, there is currently limited published evidence of MPS being utilized to study the disposition, metabolism, pharmacology, and toxicity profiles of cell therapies. This review provides an industry perspective on the nonclinical application of MPS on cell therapies, first with a focus on oncology applications followed by examples in regenerative medicine.

Plain language summary
Microphysiological systems (MPS) are advanced cell models, applied in the pharmaceutical industry to characterize novel therapies. While their application in studies of small molecule ther­apies has been very successful, the use of these models to study cell therapies has been limited. Cell therapies consist of cells and are living drugs, often with complex biological mechanisms of action, which can be very challenging to study. However, MPS have several features that make them attractive for studying cell therapies, including possibilities for longer-term studies and the ability to mimic physiologically relevant biological functions. MPS can mimic complex biological systems and processes, as such, the adoption of MPS offers a promising avenue to reduce the use of animals in the characterization of novel therapies. This review provides an industry perspective on current chal­lenges and highlights opportunities for using MPS in the development of cell therapies.

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How to Cite
Candarlioglu, P. L. (2024) “Application of microphysiological systems for nonclinical evaluation of cell therapies”, ALTEX - Alternatives to animal experimentation, 41(3), pp. 469–484. doi: 10.14573/altex.2402201.

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