Method of making human heart organoids with integrated neural crest cells

Integrating neural crest cells into human heart organoids through neurosphere incubation improves model complexity, allowing for accurate human cardiac development simulation and drug screening.

WO2026030344A1PCT designated stage Publication Date: 2026-02-05BOARD OF TRUSTEES OPERATING MICHIGAN STATE UNIV
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Patent Information

Application Number
PCT/US2025/039696
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-08-28
Filing Date
2025-07-29
Publication Date
2026-02-05

AI Technical Summary

Technical Problem

Current human heart organoid models lack neural crest cells, which are crucial for accurately modeling human heart development and disease, limiting their ability to recapitulate key aspects of human heart function and disease pathology.

Method used

A method is developed to integrate neural crest cells into human heart organoids by incubating neurospheres containing NCCs with existing heart organoids, allowing NCCs to migrate and differentiate within the organoids, forming advanced 3D models that include cardiomyocytes, epicardial cells, and other relevant cell types.

Benefits of technology

The integrated neural crest cells contribute to the cardiac conduction system, enhancing the model's complexity and accuracy in mimicking human cardiac development, enabling high-throughput drug screening and studying drug effects on cardiac development.

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Abstract

A method is provided herein for generating a human heart organoid (hHO) with integrated neural crest cells (NCCs), including incubating a neurosphere made from neural crest cells (NCCs) with an hHO, where the neurosphere is formed in a round-bottom or angled-bottom container. Additionally, the hHO has differentiated for about 11-17 days and / or expresses at least five times more Semaphorin-3C (SEMA3C) in comparison to an earlier hHO that has been differentiating for at least 48 hours less than the hHO. Also provided is an hHO with integrated NCCs prepared by the disclosed method. A method for evaluating the effects(s) of one or more drugs on hHO development and / or function by exposing NCCs to drugs, incorporating the NCCS into hHOs, and comparing drug-treated hHOs with integrated NCCs to non-drug-treated hHOs with NCCs is also provided.
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