Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies

Abstract Microphysiological systems (MPS), consisting of tissue constructs, biomaterials, and culture media, aim to recapitulate relevant organ functions in vitro. MPS components are housed in fluidic hardware with operational protocols, such as periodic complete media replacement. Such batch-like o...

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Autores principales:	Christian Maass, Matthew Dallas, Matthew E. LaBarge, Michael Shockley, Jorge Valdez, Emily Geishecker, Cynthia L. Stokes, Linda G. Griffith, Murat Cirit
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a3e52ad9c3af416aad7fb8fc0c9a0240
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spelling	oai:doaj.org-article:a3e52ad9c3af416aad7fb8fc0c9a02402021-12-02T15:08:25ZEstablishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies10.1038/s41598-018-25971-y2045-2322https://doaj.org/article/a3e52ad9c3af416aad7fb8fc0c9a02402018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25971-yhttps://doaj.org/toc/2045-2322Abstract Microphysiological systems (MPS), consisting of tissue constructs, biomaterials, and culture media, aim to recapitulate relevant organ functions in vitro. MPS components are housed in fluidic hardware with operational protocols, such as periodic complete media replacement. Such batch-like operations provide relevant nutrients and remove waste products but also reset cell-secreted mediators (e.g. cytokines, hormones) and potentially limit exposure to drugs (and metabolites). While each component plays an essential role for tissue functionality, MPS-specific nutrient needs are not yet well-characterized nor utilized to operate MPSs at more physiologically-relevant conditions. MPS-specific nutrient needs for gut (immortalized cancer cells), liver (human primary hepatocytes) and cardiac (iPSC-derived cardiomyocytes) MPSs were experimentally quantified. In a long-term study of the gut MPS (10 days), this knowledge was used to design operational protocols to maintain glucose and lactate at desired levels. This quasi-steady state operation was experimentally validated by monitoring glucose and lactate as well as MPS functionality. In a theoretical study, nutrient needs of an integrated multi-MPS platform (gut, liver, cardiac MPSs) were computationally simulated to identify long-term quasi-steady state operations. This integrative experimental and computational approach demonstrates the utilization of quantitative multi-scale characterization of MPSs and incorporating MPS-specific information to establish more physiologically-relevant experimental operations.Christian MaassMatthew DallasMatthew E. LaBargeMichael ShockleyJorge ValdezEmily GeisheckerCynthia L. StokesLinda G. GriffithMurat CiritNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christian Maass Matthew Dallas Matthew E. LaBarge Michael Shockley Jorge Valdez Emily Geishecker Cynthia L. Stokes Linda G. Griffith Murat Cirit Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies
description	Abstract Microphysiological systems (MPS), consisting of tissue constructs, biomaterials, and culture media, aim to recapitulate relevant organ functions in vitro. MPS components are housed in fluidic hardware with operational protocols, such as periodic complete media replacement. Such batch-like operations provide relevant nutrients and remove waste products but also reset cell-secreted mediators (e.g. cytokines, hormones) and potentially limit exposure to drugs (and metabolites). While each component plays an essential role for tissue functionality, MPS-specific nutrient needs are not yet well-characterized nor utilized to operate MPSs at more physiologically-relevant conditions. MPS-specific nutrient needs for gut (immortalized cancer cells), liver (human primary hepatocytes) and cardiac (iPSC-derived cardiomyocytes) MPSs were experimentally quantified. In a long-term study of the gut MPS (10 days), this knowledge was used to design operational protocols to maintain glucose and lactate at desired levels. This quasi-steady state operation was experimentally validated by monitoring glucose and lactate as well as MPS functionality. In a theoretical study, nutrient needs of an integrated multi-MPS platform (gut, liver, cardiac MPSs) were computationally simulated to identify long-term quasi-steady state operations. This integrative experimental and computational approach demonstrates the utilization of quantitative multi-scale characterization of MPSs and incorporating MPS-specific information to establish more physiologically-relevant experimental operations.
format	article
author	Christian Maass Matthew Dallas Matthew E. LaBarge Michael Shockley Jorge Valdez Emily Geishecker Cynthia L. Stokes Linda G. Griffith Murat Cirit
author_facet	Christian Maass Matthew Dallas Matthew E. LaBarge Michael Shockley Jorge Valdez Emily Geishecker Cynthia L. Stokes Linda G. Griffith Murat Cirit
author_sort	Christian Maass
title	Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies
title_short	Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies
title_full	Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies
title_fullStr	Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies
title_full_unstemmed	Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies
title_sort	establishing quasi-steady state operations of microphysiological systems (mps) using tissue-specific metabolic dependencies
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/a3e52ad9c3af416aad7fb8fc0c9a0240
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Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies

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