SLAS2021 Digital International Conference and Exhibition

Tuesday, January 26, 1–2 PM
2021 HCS/HCA Data and Informatics SIG
High content imaging approaches to organs-on-chips: recent advancements and future prospects
This guided panel discussion on Organ-on-a-Chip technology will include brief presentations by three panelists to encourage the audience to engage and participate in what we anticipate will be a lively discussion. Organs-on-chips are miniaturized 3D microfluidic devices that reconstruct the multicellular and physical microenvironment of specific tissues or organs and can be used to model normal or disease level functions. Topics will include 1) How organs-on-chips recapitulate physiological conditions and offer an alternative or parallel preclinical model to study biological mechanisms or assess drug efficacy/toxicity, 2) High content imaging assays that are being applied to organs-on-chips, and 3) Current opportunities, challenges, and development areas for the future of HCS/HCA applications using organs-on-chips platforms.

SIG panelists

Olivier Frey, PhD
Head of Technologies and Platforms
Microphysiological Systems Lead
InSphero AG

Seungil Kim, PhD
Staff Scientist, Microscopy Team Manager
USC, Ellison Institute

Lorna Ewart, PhD
Executive Vice President and Scientific Liason
Emulate, Inc.

This SIG is sponsored by SLAS and the Society of Biomolecular Imaging and Informatics (SBI2)

Presented by Judi Wardwell-Swanson, InSphero Senior Application Scientist

Abstract
In vitro spheroid models are fast becoming the de facto standard for drug discovery applications, largely due to their human-like physiological and morphological characteristics, tissue-like cellular complexity, and long functional lifespan. Each of these attributes contributes to an in vitro model platform capable of providing a more accurate reflection of patient treatment plans and responses in the clinic. High content imaging and analysis (HCA) of 3D spheroid models can provide valuable information to help researchers untangle disease pathophysiology and assess novel therapies more effectively. The transition from simple monolayer 2D cell models to dense 3D spheroids in HCI applications, however, requires 3D-optimized protocols, instrumentation, and resources.

We have identified 6 key areas, related to the broader topics of “3D Cell Models and Assays” and “3D High Content Imaging”, on which to focus while establishing a high content imaging and image analysis pipeline for complex 3D spheroid models: 1) Bio-relevant 3D spheroid models to mimic healthy and diseased physiology in vitro; 2) Scalable 3D cell assay technology to culture and conduct experiments on 3D models; 3) 3D optimized protocols to fix, stain, and clear 3D models for imaging; 4) 3D ready automation systems; 5) 3D compatible HCI systems; and 6) 3D image and Data Analysis systems to interpret and present results that provide drug discovery insights. Within each of these key areas, we share specific tips and tricks for setting up and conducting a successful proof-of-concept study designed to test the full potential of high-resolution image-based analysis of 3D spheroid models. We also provide a working checklist for researchers and core services groups planning to exploit these technologies in their work.

Presented by Olivier Frey, PhD, InSphero Head of Platforms and Technologies

Abstract
Disease modeling and drug development require an understanding of the interactive nature of different organs in the human body. Many building blocks from several research disciplines must be merged to engineer scalable multi-organ in vitro systems that can replicate systemic in vivo responses. Here we present a microphysiological 3D human liver – islet microtissue platform with automated assembly that enables direct liver – islet crosstalk for studying drug-drug interactions.

The building blocks of our multi-organ systems are: 1) Liver microtissues, which consist of a primary hepatocyte-Kupffer cell co-culture with sustained metabolic and inflammatory function for at least four weeks; 2) Islet microtissues, comprising all endocrine cells at a physiological ratio with maintained glucose response for at least four weeks; 3) Optimized co-culture medium and active liver-islet crosstalk improving viability and functional responsiveness of microtissues in insulin-free medium; 4) A scalable microfluidic multi-compartment system in SLAS/ANSI plate format with gravity-driven perfusion; and 5) A robotic liquid handler for automated and damage-free assembly of the different microtissues in the multi-organ system.

In a proof-of-concept study, we mimicked a common, drug-drug interaction occurring in cancer patients needing diabetic medication. Type 2 diabetes patients who receive the anti-diabetic drug Gliclazide have an elevated risk for life-threatening hyperglycemic conditions when co-administered with the anti-tumor drug Rifampicin. This adverse drug-drug interaction is caused by Rifampicin inducing a higher activity of drug metabolism, thereby increasing clearance rate of Gliclazide. Lower Gliclazide plasma levels lead to decreased plasma insulin concentrations and thus increased blood glucose levels in patients.

Using our multi-organ network, we replicated the effect in vitro. The drug-drug interaction was characterized by comparing insulin concentrations and gliclazide clearance between liver-islet and islet-only microphysiological co-culture. Gliclazide caused an induction of insulin secretion from islets and thereby led to a substantial increase in insulin concentration in the multi-organ system. Similar to data documented in medical reports, Rifampicin co-administration reduced the amount of active Gliclazide molecules, in turn impacting insulin secretion from islets and therefore insulin availability.