Feb 22 2019
The triumphant testing of multi-organ “human-on-a-chip” models to re-execute the 28-day experiments generally used in animals to assess the systemic toxicity of cosmetic compounds and drugs has brought the replacement of animals as test subjects a step closer to reality.
Human-on-a-chip systems aim to reproduce physiologic aspects of the human body by merging human tissue with engineered BioMEMs systems to emulate clinical parameters. This technology opens a broad spectrum of possibilities to better predict the human outcome without having to rely on animal experimentation. (Image credit: Hesperos, Inc.)
The microfluidic device has been reported and featured as a frontispiece in Advanced Functional Materials, a prestigious peer-reviewed scientific journal, and includes interlinking modules that consist of human-derived liver, heart, nervous system, and skeletal muscle cells, enabling it to maintain cellular viability and to record cellular function in real time for 28 days.
Working with the Florida biotech firm Hesperos, Inc., the University of Central Florida (UCF) has demonstrated that one of its novel four-organ in vitro (out-of-body) model systems has the potential to realistically replicate in vivo (in-body) responses to sustained drug dosing of human cells.
The technology could allow us, in the very near future, to move chronic drug experiments from animal models to these novel human in vitro models.
James J. Hickman, Chief Scientist, Hesperos, Inc.
Hickman is a Professor at UCF’s NanoScience Technology Center.
This is significant since the efficacy and toxicity of new compounds are analyzed upon both acute (single administration at high concentrations, over a short-term period) and chronic (continuous or repeated administration at lower concentrations, over an extended period) exposures. Although organ-on-a-chip models have earlier been employed for acute toxicity screening and action validation (efficacy) mechanism, they have not been appropriate for long-term studies owing to lack of organ-organ communication, short half-lives, and outcomes that are challenging to extrapolate to human organ functions.
The Hesperos system solves these drawbacks with a model that enables interaction between its small organs, which were cultured in a serum-free blood surrogate solution from real human cells, in a manner that realistically replicates responses of the system body to any compounds introduced to it. In addition, it has the ability to non-invasively assess the electrical activity of cardiac cells and neurons, and also the mechanics of skeletal and cardiac muscle contractions. Cellular function monitoring such as this proves critical in chronic toxicity testing as it mimics in vivo function.
To achieve the 28-day testing milestone, engineers at Hesperos employed computational fluid dynamic modeling to alter their prevalent multi-organ models. They reduced the size of their models, optimized their flow properties, and included more functional measurements.
We have created a valuable tool to model the pharmacokinetics and pharmacodynamics profile of known drugs, in line with ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines. In the future, it could also be used to generate mechanistic models to predict the outcome of unknown drugs, and in other precision medicine applications.
James J. Hickman, Chief Scientist, Hesperos, Inc.
The tool would prove specifically valuable to the cosmetics industry, where the use of animals to assess the toxicity of ingredients has been banned already in the European Union, and more recently in certain regions of the United States.