title: Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration.
abstract: Our goal in developing Microphysiological Systems (MPS) technology is to provide an improved approach for more predictive preclinical drug discovery via a highly integrated experimental/computational paradigm. Success will require quantitative characterization of MPSs and mechanistic analysis of experimental findings sufficient to translate resulting insights from in vitro to in vivo. We describe herein a systems pharmacology approach to MPS development and utilization that incorporates more mechanistic detail than traditional pharmacokinetic/pharmacodynamic (PK/PD) models. A series of studies illustrates diverse facets of our approach. First, we demonstrate two case studies: a PK data analysis and an inflammation response--focused on a single MPS, the liver/immune MPS. Building on the single MPS modeling, a theoretical investigation of a four-MPS interactome then provides a quantitative way to consider several pharmacological concepts such as absorption, distribution, metabolism, and excretion in the design of multi-MPS interactome operation and experiments.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Cilfone
authors.affiliation: CN Bio Innovations Welwyn Garden City, UK.
authors.forename: E M
authors.initials: EM
authors.lastname: Large
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
authors.forename: U
authors.initials: U
authors.lastname: Sarkar
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Wishnok
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA ; Department of Chemistry, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Tannenbaum
authors.affiliation: CN Bio Innovations Welwyn Garden City, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Hughes
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Lauffenburger
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA ; Center of Gynepathology, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
authors.forename: L G
authors.initials: LG
authors.lastname: Griffith
authors.affiliation: Stokes Consulting Redwood City, California, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Stokes
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cirit