Important Considerations for Human-Relevant Models

Danaher

Human-relevant models and spatial profiling are transforming drug discovery by offering more predictive, human-like data than traditional animal models and 2D cultures. Human-relevant models, such as organoids and 3D cell cultures, better mimic human biology, improving disease modeling, drug screening and precision medicine.

Spatial profiling further improves these insights by mapping cellular interactions and biomarker distribution, supporting personalized treatments for cancer, neurodegenerative diseases and autoimmune disorders.

These methods decrease dependence on animal testing, aligning with regulatory shifts and improving early toxicity assessments. By bridging the gap between preclinical research and clinical trials, human-relevant models and spatial profiling accelerate drug development, ensuring safer more effective treatments reach patients faster.

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Translatability and scalability in different cellular model systems

The expense of screening and developing drug candidates necessitates cost-effective technologies that can more accurately recapitulate human physiology and response. Currently, screening potential candidates is primarily accomplished through simple bioassays and animal models. While these approaches provide information on drug safety, toxicity, efficacy and pharmacokinetic action, they have inherent limitations. This is evident by the high drug failure rate during clinical trials.

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High clinical trial failure rates

Preclinical models often produce data that don’t accurately reflect human physiological responses

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Limited translatability

Simple bioassays and animal models lack the complexity of human biology, reducing relevance and reliable data

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High cost

Animal studies are costly, which limits scalability, requires significant resources and raises ethical concerns

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Need for better models

The need for more relevant data earlier in drug development highlights a need for preclinical models that enable high-throughput screening of multiple candidates

The drug discovery and development fields are eagerly adopting microphysiological systems, such as organoids, to augment their research and offset clinical translation issues. These systems offer several key advantages:

Improved physiological relevance – Accurately represents human physiology and pathology better than simple monolayer cell cultures
Ethical benefits – Organoids reduce the reliance on animal testing and align with societal preferences for humane research practices
Regulatory recognition – Recognized as a New Alternative Method in drug development by the FDA Modernization Act 2.0
Versatile applications – Serve as a valuable platform for small and large molecule testing, safety screening, toxicity and biomarker discovery

Immortalized cell lines are widely used in drug discovery due to their well-characterized properties, ability to mimic diseases and ease of manufacturing. This makes them suitable for disease recapitulation and identification in cell-based models. However, limitations in translatability were encountered. In contrast, patient-derived organoids offer improved translatability as they closely resemble their tissue of origin, making them more physiologically relevant and better at predicting therapeutic outcomes.

Long-term live imaging of 3D human-relevant models

Researchers use 3D imaging to study the development and dynamics of complex biological systems in detail, down to the single-cell level. This can reveal differences resulting from experimental manipulations or compare the control and treatment. For example, the presence or absence of specific cells or changes to their morphology (e.g., shape, volume, length, area, etc.) are informative parameters. As a particularly gentle imaging technique, light sheet microscopy provides an unbiased view of processes over time. Light sheet microscopy is well suited for thick, delicate or dynamic samples such as tumoroids, spheroids or organoids. The noninvasive nature and its ability to acquire 3D data make it well-suited for time-lapse imaging studies. Light sheet microscopy can increase our understanding of complex biological systems in developmental biology, neuroscience, cell biology, drug discovery, cancer research and other fields.

Light sheet microscopy is a technique enabling imaging of organoids and larger samples. It excites the sample parallel to the focal plane, perpendicular to the detection objective, providing optical sectioning with a thin excitation plane. This reduces phototoxicity and photobleaching while allowing high-speed imaging. For long-term imaging of human-relevant models, minimizing phototoxicity is crucial to prevent ROS generation and thermal damage from intense laser exposure.

Experience the key benefits of imaging large and complex samples with Leica Microsystems’ light sheet microscopy solutions:

Capture sharp, uniformly illuminated images of large-volume specimens over extended periods
Easily mount samples and maintain experimental protocols with minimal disruption
Make on-the-fly adjustments during experiments for greater flexibility and convenience
Choose from stand-alone systems or integrated solutions for fast, gentle volumetric imaging
Study complex samples such as patient-derived tumoroids, spheroids and organoids with reliable, precise and versatile technology
Push the boundaries of research with advanced imaging tools and AI-driven analysis software designed for high performance and reproducibility

The life sciences companies of Danaher provide integrated solutions for human-relevant models and spatial profiling, addressing the need for more predictive models in drug discovery. Contact an expert today to learn how to enhance data accuracy, optimize drug response insights and drive the next generation of precision medicine.