The Vision for Multi-organ Human-on-a-Chip Models
The development of organ-on-a-chip models aims to reduce the (expensive) high drug failure rates that exist in clinical trials.
While some models have enabled some level of efficacy assessment and toxicity screening, they have not been suitable for long-term studies.
In collaboration with the University of Central Florida, a Florida biotech firm called Hesperos Inc. recently reported that their multi-organ “human-on-a-chip” system maintains cellular viability over 28 days in serum-free conditions, using a pumpless system. The study was published in Advanced Functional Materials.
To learn more about the vision for multi-organ “human-on-a-chip” models, we caught up with James Hickman, Chief Science Officer of Hesperos Inc.
Michele Wilson (MW): Can you tell us about Hesperos and its mission?
James Hickman (JH): Hesperos Inc. provides insights into novel drug candidates at the preclinical stage by evaluating their efficacy and safety using sensitive, functional readouts in a human-on-a-chip multiorgan model. This new technology is helping pharmaceutical researchers, large and small, make more informed decisions on which drugs to move forward with, ultimately bringing patients new therapeutics cheaper and quicker than ever possible before.
The mission of Hesperos is to revolutionize toxicology testing as well as efficacy evaluation for drug discovery. In pursuit of this mission, the company has created pumpless platforms with serum-free cellular mediums that allow multi-organ system communication and integrated computational modeling of live physiological responses of functional neurons, cardiac, muscle, and neuromuscular junctions as well as liver, pancreas and barrier tissues.
MW: How did you go about selecting the different tissues that are featured on the microfluidic device?
JH: Hesperos works closely with pharmaceutical partners to understand their drug testing goals, using that information to inform their selection of tissues in the device.
JH: The use of serum has many drawbacks, including batch-to batch-variability and its undefined contents. This is because serum is collected from calf fetuses in a slaughterhouse, in most cases with no quality control. These drawbacks make reproducibility and transferability of data collected by its use difficult.
We have created a serum-free medium formulation that enables the in vitro culturing of a wide range of cell types up through several weeks. This formulation supports cardiomyocytes, multiple cancer lines, hippocampal neurons, motoneurons (MNs), sensory neurons, skeletal muscle, NMJ (neuromuscular junction) formation, hepatocytes, endothelial and epithelial cells, among others. For obvious reasons, we hold the detailed formulation close to our chest.
MW: While animal models have their limitations, in vitro models do too – do you think that human-on-a-chip models can remove the need for animal research in some settings?
While we do believe these human MPS models will eventually replace animal testing, there are quite a few hurdles to overcome before this can happen. Some of those hurdles are scientific, including the further development of certain organ models or, in some cases, increasing the complexity or architecture of current models. Others include changing the regulatory mindset towards acceptance and reliance on the data generated. In the short term, we believe these systems are meant to supplement animal models and eventually to replace them or limit them to early rodent toxicology studies.
JH: We agree that there is significant heterogeneity between groups of people and this should be accounted for in the validation of these models. One of the beauties of these systems is that we can use human iPSCs (induced pluripotent stem cells) to derive certain phenotypes, or even samples from individual patients, and test molecules based on those groupings. For example, currently some drug compounds such as warfarin come with a black box warning that requires a genetic phenotyping to determine whether you are a high, low, or intermediate metabolizer of the compound based on point mutations in the CYP2C9 gene, which unfortunately was discovered after the fact. It is possible to test variants such as those within these MPS models and identify potential populations at risk, as well as tailor the therapeutic index per population.
MW: What has been the biggest challenge in the development process, and how did you overcome it?
The second is getting the industry and the FDA to fully realize the usefulness of these systems and change the dogma surrounding drug development approaches; there is steady progress towards the acceptance of human-on-a-chip models in drug discovery.