In This Section

Novel Microphysiological and Microtissue Systems to Advance Transporter Research

Saturday April 02, 2022

1:30 pm - 3:00 pm Eastern Time (ET)

113 C

DMDD TOX

Chair :

Lauren Aleksunes
Rutgers University



Recent advances in the development of novel testing systems that recapitulate the human microenvironment and microanatomy have advanced drug and chemical screening. Using microphysiological systems, investigators are able to consider the influence of fluid flow, cell-cell communication, extracellular matrix, and 3-dimensional organization in organs-on-a-chip and tissue-engineered organ constructs and microtissues. Advancement of this technology includes the robust characterization of transporter expression and function, often in concert with evaluation of drug metabolizing enzymes and regulatory factors. This session will highlight examples of microfluidic systems and novel tissue cultures that recapitulate human transporter function across a number of organ systems. Speakers will review the potential application of these model systems for drug development and toxicity screening.

Speakers

Catherine Yeung - University of Washington

Renal Transporter Function and Chronic Kidney Disease: Utility of a Dual-Channel Microphysiological System

The kidney proximal tubule is responsible for the clearance of many drugs and toxins; this role also renders it highly vulnerable to injury. We have used a dual-channel vascularized proximal tubule epithelial cell microphysiologic system (MPS) to model the OAT1/3 mediated renal clearance of compounds including para-aminohippurate and morphine/morphine metabolites and successfully used MPS in vitro parameters to predict human renal clearance. In addition, have also identified a multi-step mechanism of Ochratoxin A nephrotoxicity involving OATs, cytochrome P450s, and GSTs using kidney MPS technology.

Seyoum Ayehunie - MatTek

Novelty of 3D Human Gut Microtissues as a Holistic Tissue Model for Drug Absorption and Metabolism

Availability of human primary cell-based 3D human small intestinal microtissues that recapitulate structural, efflux and influx transporters, and show functional mimicry with the in vivo counterpart is critical to obtain predictive and reproducible in vitro testing tool for drug development. An in vitro intestinal tissue model that expresses the relevant drug transporters and drug metabolizing enzymes, such as ABCB1/MDR1/P-gp, ABCC1/MRP1, ABCC2/MRP2, and ABCG2/BCRP, CYP3A4, CYP2J2, UDP-glucuronosyltransferases, and carboxylesterases will mitigate drug discovery challenges across the pharmaceutical industry and advance screening of xenobiotic compounds intended for oral administration. These 3D human gut models will also bridge the gap in preclinical testing by providing a more predictive in vitro drug testing platform.

Pouria Fattahi

Placenta-on-a-Chip to Evaluate Maternal-Fetal Chemical Transfer

The placenta is an important regulator of fetal exposure to chemicals. We present a novel microengineered biomimetic platform to investigate the maternal-to-fetal transfer of heavy metals in the human placenta with focus on the role of the BCRP/ABCG2 transporter.

Christopher Arian - University of Washington

Abstract #4064 - The Development of an Intestinal Microphysiological System to Model Oral Drug Disposition