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Updated: Aug 19, 2025
Generating Self-Assembling Human Heart Organoids Derived from Pluripotent Stem Cells
Published on: September 15, 2021
Wnt signaling directs human pluripotent stem cells into vascularized cardiac organoids with chamber-like structures
Po-Yu Liang1, Yun Chang1,2, Gyuhyung Jin1,2
1Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, United States.
Insights
Researchers developed advanced 3D cardiac organoids using human pluripotent stem cells (hPSCs). These organoids mimic heart structures, improving disease modeling and drug testing for cardiovascular conditions.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Biomaterials Science
Background:
- Heart disease is a global health crisis.
- Human pluripotent stem cells (hPSCs) offer potential for disease modeling and drug screening.
- Current hPSC-derived cardiac organoids lack native-like structural maturity.
Purpose of the Study:
- To develop mature cardiac organoids with native-like structures.
- To improve cardiovascular disease modeling and cardiotoxic drug screening in vitro.
- To investigate the role of spatiotemporal signaling in cardiac organoid development.
Main Methods:
- Temporal modulation of the Wnt signaling pathway.
- Co-differentiation of hPSCs into cardiomyocytes and cardiac endothelial-like cells.
- Formation of 3D cardiac organoids with endothelial-bounded chambers.
Main Results:
- Achieved cardiac endothelial-bounded chamber formation in 3D organoids.
- Chambered organoids showed more mature membrane potential than cardiomyocyte-only organoids.
- Enhanced response to cardiotoxic drugs observed in chamber-containing organoids.
Conclusions:
- Spatiotemporal signaling modulation can yield more mature cardiac organoids.
- These advanced organoids enhance cardiovascular disease study and drug evaluation.
- This approach holds promise for regenerative medicine and personalized therapies.
Abstract:
Heart diseases are leading cause of death around the world. Given their unique capacity to self-renew and differentiate into all types of somatic cells, human pluripotent stem cells (hPSCs) hold great promise for heart disease modeling and cardiotoxic drug screening. hPSC-derived cardiac organoids are emerging biomimetic models for studying heart development and cardiovascular diseases, but it remains challenging to make mature organoids with a native-like structure in vitro. In this study, temporal modulation of Wnt signaling pathway co-differentiated hPSCs into beating cardiomyocytes and cardiac endothelial-like cells in 3D organoids, resulting in cardiac endothelial-bounded chamber formation. These chambered cardiac organoids exhibited more mature membrane potential compared to cardiac organoids composed of only cardiomyocytes. Furthermore, a better response to toxic drugs was observed in chamber-contained cardiac organoids. In summary, spatiotemporal signaling pathway modulation may lead to more mature cardiac organoids for studying cardiovascular development and diseases.
