Enhancing Drug Screening With Human-Relevant Models
Discover how advanced tissue models and AI are reshaping drug screening with more predictive, human-relevant systems.
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Traditional preclinical models often fail to accurately replicate human physiology, contributing to high drug failure rates in clinical trials. Microphysiological systems (MPS) integrate multiple human cell types within a physiologically relevant environment, mimicking key biological functions like vascular flow and tissue organization. As pharmaceutical companies embrace more complex therapeutic modalities, the demand for scalable, predictive MPS models continues to grow.
Technology Networks recently spoke with Sebastiaan J. Trietsch, Chief Technology Officer at MIMETAS, to discuss the evolving role of MPS in drug discovery. He shared insights into how advanced tissue models are enhancing physiological relevance and scalability and highlighted the increasing integration of MPS with AI-driven phenotypic screening, a shift that could reshape preclinical drug development.
Microphysiological Systems (MPS) have gained significant traction in drug discovery. What has been the major driver of this growth?
Sebastiaan J. Trietsch, PhD (SJT):
The vast majority of drugs fail in human trials due to the poor predictivity of preclinical models. Traditional models – whether simple cell cultures in petri dishes or animal models – often fail to accurately reflect human physiology, leading to costly R&D setbacks and fewer effective treatments reaching patients.
MPS bridge this gap and embrace the complexity of human physiology by combining multiple cell types – epithelial, vascular, connective tissue and immune cells – alongside key physiological elements such as flow dynamics and a 3D extracellular matrix. The pharmaceutical industry recognizes that diseases become apparent at the interplay between cell types and is embracing MPS in their drug discovery trajectories. Additionally, the rise of novel drug modalities has further accelerated the adoption of MPS, as these advanced systems can model complex human-specific responses that traditional models cannot capture.
KR:
With increasing interest in physiologically accurate tissue models, how do you see the future of MPS evolving in drug discovery and disease research?
SJT:
MPS are poised to become a cornerstone technology for understanding disease mechanisms and developing new therapies. Over the next five years, we expect the biggest impact to come from organ-specific models – both healthy and diseased – that can provide unprecedented physiological insights and improve drug screening outcomes. Although multi-organ chips and 'body-on-a-chip' technologies remain an area of interest, we believe the immediate transformation will be driven by advanced single-organ models with superior predictive power. The most compelling reason for this shift is the ability of MPS to deliver physiologically relevant data at high throughput.
At MIMETAS, we are developing models and assays for key organs such as the lung, liver, kidney, brain and gut, as well as cancer and vasculature. We offer such solutions by combining fully vascularized tissue made using patient-derived organoids, including connective tissue, immune cells and stromal components. When deployed at scale using lab automation and AI-driven analysis, these advanced models enable drug development at an industrial scale, accelerating the discovery of effective treatments more efficiently than any alternative technology.
KR:
What are the current limitations of traditional flow-based drug discovery systems, and how does the OrganoPlate® UniFlow (UF) address these challenges?
SJT:
Traditional flow-based drug discovery systems often rely on complex tubing and external pumps, making them difficult to scale and limiting their accessibility.
Our Uniflow technology overcomes these limitations with a gravity-driven, pump-free system that provides continuous, unidirectional flow, effectively mimicking vascular dynamics while maintaining physiological shear stress. This innovative design leads to more realistic tissue behavior and enhances the predictive power of disease models.
KR:
How does the OrganoPlate UF enhance scalability and high-throughput screening capabilities?
SJT:
The OrganoPlate UF is based on a standard microtiter plate format that is pipette operatable and fully compatible with robots and automated microscopes. Each plate comprises up to 48 chips allowing proper controls and parameter variations on a single plate.
Flow within the OrganoPlate is actuated through tilting-based leveling, facilitated by the OrganoFlow device, which precisely tilts the plate at set intervals to maintain controlled fluid dynamics. Unlike the original OrganoPlate, which supports only bi-directional flow, the UniFlow technology introduces unidirectional flow via a reset channel, more accurately replicating physiological circulation.
This platform preserves the throughput, compatibility and usability of the original OrganoPlate platform while enhancing physiological relevance. In fact, the platform is fully automatable allowing screens with thousands of molecules on tissue models that are unrivalled in terms of physiological relevance.
KR:
What do you see as the next frontier in microphysiological disease modelling?
SJT:
The coming years will see the continued expansion of more complex and comprehensive MPS models in drug discovery. We anticipate significant advances in the integration of MPS with reference datasets to enable AI assisted phenotypic screening.
As these models demonstrate their value in preclinical drug testing, we expect to see MPS-driven clinical successes, with validated models influencing regulatory frameworks for safety assessments – particularly for emerging drug modalities. Ultimately, MPS will play a pivotal role in shaping next-generation drug development, bridging the gap between preclinical research and clinical outcomes more effectively than ever before.
