03124nas a2200337   4500000000100000000000100001008004100002260001500043653001000058653003500068653002100103653003000124653002600154100002600180700001900206700002000225700001700245700002400262700001400286700001600300700002200316700002000338700001600358700001600374245009100390856005600481300001200537490000700549520221600556022001402772       2024                            d  c2024-07-1610aCAR T10acomplex in vitro models (CIVM)10aDrug development10ahuman model systems (HMS)10aRegenerative Medicine1 aPelin L. Candarlioglu1 aLouise Delsing1 aLauren Gauthier1 aLauren Lewis1 aGeorge Papadopoulos1 aMay Freag1 aTom S. Chan1 aKimberly A. Homan1 aMick D. Fellows1 aAmy Pointon1 aKyle Kojala00aApplication of microphysiological systems for nonclinical evaluation of cell therapies  uhttps://altex.org/index.php/altex/article/view/2767  a469-4840 v413 aMicrophysiological 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.  a1868-8551