Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies
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s41598-018-25971-y.pdf
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Author(s)
Dallas, Matthew
Stokes, Cynthia L.
Maass, Christian Alexander
LaBarge, Matthew E
Shockley, Michael J
Valdez Macias, Jorge Luis
Geishecker, Emily R
Griffith, Linda G
Cirit, Murat
Date Issued
May 2018
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Maass, Christian, Matthew Dallas, Matthew E. LaBarge, Michael Shockley, Jorge Valdez, Emily Geishecker, Cynthia L. Stokes, Linda G. Griffith, and Murat Cirit. “Establishing Quasi-Steady State Operations of Microphysiological Systems (MPS) Using Tissue-Specific Metabolic Dependencies.” Scientific Reports 8, no. 1 (May 22, 2018).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Biotechnology Process Engineering Center
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/s41598-018-25971-y
