Challenges and opportunities toward enabling phenotypic screening of complex and 3D cell models

Area of Science:

• Biotechnology
• Drug Discovery
• Cellular Models

Background:

• Conventional 2D cell systems are increasingly being replaced by advanced organotypic cellular platforms in drug discovery.
• Organotypic cellular platforms provide a more physiologically relevant environment for studying drug efficacy and toxicity.

Purpose of the Study:

• To provide an industry-centric review of complex cell models in drug discovery.
• To discuss the benefits, challenges, and opportunities of incorporating multidimensional cell platforms into high-density screening formats.
• To highlight the need for novel technologies to support the integration of these advanced models.

Main Methods:

• Review of current literature and industry trends in cellular models for drug discovery.
• Analysis of the advantages of complex cell models (e.g., 3D structures) over traditional 2D systems.
• Discussion of technological requirements for high-density screening formats.

Main Results:

• Complex cell models offer significant advantages over conventional 2D systems for drug discovery.
• Challenges include the need for real-time, noninvasive quantification of 3D structures.
• Opportunities lie in using focused chemical and genomics libraries with primary and induced pluripotent stem cell-derived models.

Conclusions:

• Organotypic cellular platforms represent a significant advancement in drug discovery.
• Development of novel chemical sensors and targeted libraries is crucial for widespread adoption.
• Emerging technologies hold promise for integrating complex cell systems into mainstream drug screening pipelines.