Human Pluripotent Stem-Cell-Derived Models as a Missing Link in Drug Discovery and Development

Area of Science:

• Biotechnology
• Stem Cell Biology
• Drug Discovery

Background:

• Human pluripotent stem cells (hPSCs), encompassing human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs), are pivotal in advancing pharmaceutical research.
• The integration of hPSC-derived models into drug discovery pipelines presents a significant opportunity to enhance efficiency and success rates.

Purpose of the Study:

• To review the multifaceted applications of hPSC-derived in vitro models across all stages of the drug discovery and development process.
• To highlight the utility of patient-derived or genome-edited hPSCs in creating disease-specific models for research and therapeutic development.

Main Methods:

• Analysis of existing literature and case studies on hPSC applications in drug discovery.
• Examination of various stages including phenotypic screening, target-based screening, target validation, toxicology, precision medicine, and clinical trials.

Main Results:

• hPSC-derived models are actively employed in phenotypic and target-based screening, target validation, and toxicology evaluations.
• These models facilitate precision medicine approaches, 'clinical trials in a dish,' and post-clinical studies, offering insights into disease mechanisms and drug efficacy.
• Patient-specific and genome-edited hPSCs enable the development of robust in vitro models for comprehensive drug evaluation.

Conclusions:

• hPSC-derived in vitro models significantly contribute to dissecting disease mechanisms, identifying drug targets, and screening drug candidates.
• These advanced models are crucial for preclinical and post-clinical assessment of drug safety and efficacy.
• Continued advancements in biotechnology and developmental biology promise to further enhance the cost-effectiveness and success rates of drug discovery and development using hPSC technology.