Human Cardiac Organoids: Advances and Prospects from Construction to Preclinical Drug Evaluation

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Drug Development

Background:

• Drug-induced cardiotoxicity (DICT) poses significant risks to patient safety and drug development.
• Existing preclinical models lack the predictive power needed for complex cardiovascular diseases.
• Human pluripotent stem cell-derived cardiac organoids (hCOs) show promise in mimicking human heart structure and function.

Purpose of the Study:

• To present a holistic framework for constructing and utilizing hCO-based pathological models for drug safety assessment.
• To bridge construction technology, pathological modeling, and application evaluation in a unified approach.
• To guide the development of more reliable and human-relevant preclinical drug testing paradigms.

Main Methods:

• Systematic categorization of three strategies for building hCO pathological models: patient-specific, gene-edited, and microenvironment-modulated.
• Review of hCO advantages in preclinical drug assessment, including early DICT warning, metabolism-related safety, and personalized drug evaluation.
• Discussion of current challenges (maturation, standardization) and future directions (organ-on-a-chip, AI integration).

Main Results:

• hCOs offer significant progress in simulating human heart complexity for in vitro modeling.
• Three distinct strategies enable the creation of hCO-based pathological models.
• hCOs demonstrate unique advantages for various preclinical drug safety evaluations.

Conclusions:

• A novel framework integrating construction, pathological modeling, and application evaluation for hCOs is proposed.
• hCOs represent a promising avenue for enhancing the prediction of drug-induced cardiotoxicity.
• Addressing challenges and integrating emerging technologies will further optimize hCOs for drug development.