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

## TL;DR

This review outlines how human cardiac organoids can improve drug testing by offering more accurate and personalized models of heart disease.

## Contribution

The paper introduces a novel integrated framework for human cardiac organoids that connects construction, modeling, and drug evaluation.

## Key findings

- Human cardiac organoids outperform traditional models in predicting drug-induced cardiotoxicity.
- Three strategies for building pathological models are summarized: patient-specific, gene-edited, and microenvironment-modulated.
- hCOs support early warning, metabolism-related safety, and personalized drug response assessments.

## Abstract

What are the main findings?
This review proposes an integrated research framework for human cardiac organoids (hCOs) encompassing construction technology, pathological modeling, and application evaluation, and summarizes three pathological model construction strategies: patient-specific, gene-edited, and microenvironment-modulated.hCOs demonstrate superior sensitivity and accuracy in predicting drug-induced cardiotoxicity compared to traditional models, particularly in early warning, metabolism-related safety evaluation, and personalized drug response assessment.

This review proposes an integrated research framework for human cardiac organoids (hCOs) encompassing construction technology, pathological modeling, and application evaluation, and summarizes three pathological model construction strategies: patient-specific, gene-edited, and microenvironment-modulated.

hCOs demonstrate superior sensitivity and accuracy in predicting drug-induced cardiotoxicity compared to traditional models, particularly in early warning, metabolism-related safety evaluation, and personalized drug response assessment.

What are the implications of the main findings?
hCOs provide highly faithful disease models and platforms for individualized drug efficacy evaluation and offer valuable tools for studying complex cardiovascular diseases and rare disorders.Supported by a regulatory landscape increasingly favoring non-animal testing, hCOs, coupled with emerging technologies, hold promise for reshaping preclinical drug development into a more predictive paradigm.

hCOs provide highly faithful disease models and platforms for individualized drug efficacy evaluation and offer valuable tools for studying complex cardiovascular diseases and rare disorders.

Supported by a regulatory landscape increasingly favoring non-animal testing, hCOs, coupled with emerging technologies, hold promise for reshaping preclinical drug development into a more predictive paradigm.

Drug-induced cardiotoxicity (DICT) severely hampers drug development and threatens patient safety. Together with the growing global burden of cardiovascular disease, there is an urgent need to establish more predictive preclinical models. Recently, human pluripotent stem cell-derived cardiac organoids (hCOs) have emerged as a promising three-dimensional in vitro model, achieving significant progress in simulating the complex structure and function of the human heart. However, existing reviews predominantly focus on technical construction or specific applications, lacking an integrated discussion of pathological model construction and their use under evolving regulatory frameworks. This review distinguishes itself by proposing a novel, holistic framework that bridges “construction technology,” “pathological modeling,” and “application evaluation.” We systematically categorize and summarize three major strategies for building hCO-based pathological models: patient-specific, gene-edited, and microenvironment-modulated approaches. Furthermore, we highlight the unique advantages of hCOs in preclinical drug assessment and detail their cutting-edge applications in early DICT warning, metabolism-related safety evaluation, and personalized drug evaluation. Finally, we address current challenges, including maturation and standardization, and outline future directions involving integration with organ-on-a-chip technology and artificial intelligence. This review aims to provide a theoretical foundation and roadmap toward more reliable and human-relevant drug development paradigms.