ArticleJournal of tissue engineering and regenerative medicine2021
Targeting HIF-α for robust prevascularization of human cardiac organoids.
Article in Journal of tissue engineering and regenerative medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- Integrating Bioprinting and Increased Throughput: Next-Generation Models for Cardiac Research.International journal of molecular sciences · 2025Review
- Review
- Hypoxia and Multilineage Communication in 3D Organoids for Human Disease Modeling.Biomimetics (Basel, Switzerland) · 2025Review
- Article
- Advances in cardiac organoid research: implications for cardiovascular disease treatment.Cardiovascular diabetology · 2025Review
- Engineering the 3D structure of organoids.Stem cell reports · 2025Review
- Advancing Cardiac Organoid Engineering Through Application of Biophysical Forces.IEEE reviews in biomedical engineering · 2024Article
- Potential Use of Organoids in Regenerative Medicine.Tissue engineering and regenerative medicine · 2024Review
- Mechanical strategies to promote vascularization for tissue engineering and regenerative medicine.Burns & trauma · 2024Review
- Decellularized heart extracellular matrix alleviates activation of hiPSC-derived cardiac fibroblasts.Bioactive materials · 2024Article
- Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts.Science advances · 2023Article
- Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models.International journal of molecular sciences · 2023Review
- Heart in a dish - choosing the right in vitro model.Disease models & mechanisms · 2023Article
- Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases.Frontiers in pharmacology · 2022Review
- Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering.Frontiers in bioengineering and biotechnology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Prevascularized 3D microtissues have been shown to be an effective cell delivery vehicle for cardiac repair. To this end, our lab has explored the development of self-organizing, prevascularized human cardiac organoids by co-seeding human cardiomyocytes with cardiac fibroblasts, endothelial cells, and stromal cells into agarose microwells. We hypothesized that this prevascularization process is facilitated by the endogenous upregulation of hypoxia-inducible factor (HIF) pathway in the avascular 3D microtissues. In this study, we used Molidustat, a selective PHD (prolyl hydroxylase domain enzymes) inhibitor that stabilizes HIF-α, to treat human cardiac organoids, which resulted in 150 ± 61% improvement in endothelial expression (CD31) and 220 ± 20% improvement in the number of lumens per organoids. We hypothesized that the improved endothelial expression seen in Molidustat treated human cardiac organoids was dependent upon upregulation of VEGF, a well-known downstream target of HIF pathway. Through the use of immunofluorescent staining and ELISA assays, we determined that Molidustat treatment improved VEGF expression of non-endothelial cells and resulted in improved co-localization of supporting cell types and endothelial structures. We further demonstrated that Molidustat treated human cardiac organoids maintain cardiac functionality. Lastly, we showed that Molidustat treatment improves survival of cardiac organoids when exposed to both hypoxic and ischemic conditions
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.