{"doi":"10.1093/eurheartj/ehad841","title":"Human heart organoids: current applications and future perspectives","abstract":"Cardiovascular disease (CVD) stands as the leading cause of death globally, causing 18 million deaths per year annually.1 Conventionally, animal and cellular models have been extensively used to investigate mechanisms of CVD, establish cardiac safety, and develop new therapies. Nonetheless, ∼90% of drugs developed in animal models fail in clinical trials, ∼45% due to unanticipated human toxicity, particularly cardiotoxicity. The limitations of current models highlight the urgent need for more sophisticated tools to investigate human diseases and accelerate the translation of research from bench to bedside. Over the last decade, and owing to significant advances in stem cell technologies, organoids have emerged as powerful tools in this respect. Organoids are three-dimensional, miniature organ-like structures that mimic the architecture and function of real organs, providing a more physiologically relevant model for research compared with traditional two-dimensional cell cultures. Efforts to create human heart organoids (hHOs) date back to the mid-2010s, but only recently have significantly faithful models been achieved.2,3 The delay, compared with other organoid types, can be attributed to the unique challenges posed by cardiac tissue, such as anatomical complexity and biomechanics. However, in 2021 this barrier was surpassed, and we saw the emergence, in a short period of time, of several protocols to generate advanced hHOs from human pluripotent stem cells (PSCs).4,5 Combining developmental biology and bioengineering, these organoids emphasized the self-organizing capability of PSCs. By mimicking key stages of embryonic development, hHOs were guided to form atrial and ventricular cardiomyocytes, first and second heart fields, epicardial and endocardial cells, cardiac fibroblasts, endothelial cells, and distinct cardiac chambers.4,5 Furthermore, these organoids were highly functional in electrophysiological and metabolic terms and were successfully employed to model congenital heart disease (CHD) due to genetic defects as well as maternal and environmental conditions (e.g. diabetes during gestation).4,5 Human heart organoids offer groundbreaking potential in investigating CVD and cardiac pharmacology. They allow for the precise and unrestricted study of early disease progression in a human setting and allow us to bypass any potential ethical limitations to work with disease-relevant material from humans since patient-specific induced PSCs (iPSCs) can be obtained from a blood sample. These are important features to drive human-centric mechanistic studies and precision and personalized medicine approaches. Unlimited amounts of organoids can be generated in a scalable fashion, with high reproducibility in recent protocols, enabling big pharma compound discovery screenings and safety testing. Another positive side effect of the adoption of this technology is reduced reliance on animal models. Figure 1 summarizes current and future applications of hHO technologies. Applications and future promises of human heart organoids for cardiovascular research. Created with BioRender.com By mimicking the early stages of heart development, hHOs can advance our understanding of the effects of teratogens, environmental factors such as diet, and genetic mutations. Additionally, organoids can be used to interrogate the safety of pregnancy-approved drugs taken by mothers during gestation and evaluate the effects of these drugs on cardiac development, addressing urgent clinical questions about drug safety during pregnancy and new origins of CHD6—a significant problem as most of CHD is assumed not to be from genetic origins. Managing a mother’s pre-existing conditions (e.g. depressive disorders) during pregnancy remains challenging since untreated conditions can affect maternal health negatively, while treatment with the required drugs may significantly increase the incidence of CHD in the foetus. In this context, hHOs present an unprecedented oppor","journal":"European Heart Journal","year":2023,"id":341997,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":616014,"name":"Brett Volmert","orcid":"0000-0002-5209-4833","position":1,"is_corresponding":false},{"id":616019,"name":"Aitor Aguirre","orcid":"0000-0002-1383-2792","position":2,"is_corresponding":false},{"id":278558,"name":"Aleksandra Kostina","orcid":"0000-0002-1983-4609","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T01:11:08.077724Z","pmid":"38103210","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}