ArticleMolecular therapy. Methods & clinical development2020
Delta-1 Functionalized Hydrogel Promotes hESC-Cardiomyocyte Graft Proliferation and Maintains Heart Function Post-Injury.
Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Hydrogels in cardiac tissue engineering: application and challenges.Molecular and cellular biochemistry · 2025Review
- Research Advances in Myocardial Infarction Repair and Cardiac Regenerative Medicine via the Notch Signaling Pathway.Reviews in cardiovascular medicine · 2025Review
- Genetically Encoded XTEN-based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Epigenetic determinants and non-myocardial signaling pathways contributing to heart growth and regeneration.Pharmacology & therapeutics · 2024Review
- Challenges and perspectives of heart repair with pluripotent stem cell-derived cardiomyocytes.Nature cardiovascular research · 2024Review
- Engineering tissue morphogenesis: taking it up a Notch.Trends in biotechnology · 2022Review
- Bioengineering Systems for Modulating Notch Signaling in Cardiovascular Development, Disease, and Regeneration.Journal of cardiovascular development and disease · 2021Review
- Cell augmentation strategies for cardiac stem cell therapies.Stem cells translational medicine · 2021Review
- Injectable Hydrogels for Improving Cardiac Cell Therapy-In Vivo Evidence and Translational Challenges.Gels (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Current cell transplantation techniques are hindered by small graft size, requiring high cell doses to achieve therapeutic cardiac remuscularization. Enhancing the proliferation of transplanted human embryonic stem cell-derived cardiomyocytes (hESC-CMs) could address this, allowing an otherwise subtherapeutic cell dose to prevent disease progression after myocardial infarction. In this study, we designed a hydrogel that activates Notch signaling through 3D presentation of the Notch ligand Delta-1 to use as an injectate for transplanting hESC-CMs into the infarcted rat myocardium. After 4 weeks, hESC-CM proliferation increased 2-fold and resulted in a 3-fold increase in graft size with the Delta-1 hydrogel compared to controls. To stringently test the effect of Notch-mediated graft expansion on long-term heart function, a normally subtherapeutic dose of hESC-CMs was implanted into the infarcted myocardium and cardiac function was evaluated by echocardiography. Transplantation of the Delta-1 hydrogel + hESC-CMs augmented heart function and was significantly higher at 3 months compared to controls. Graft size and hESC-CM proliferation were also increased at 3 months post-implantation. Collectively, these results demonstrate the therapeutic approach of a Delta-1 functionalized hydrogel to reduce the cell dose required to achieve functional benefit after myocardial infarction by enhancing hESC-CM graft size and proliferation.
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