Sustained miRNA delivery from an injectable hydrogel promotes cardiomyocyte proliferation and functional regeneration after ischaemic injury
Open accessAbstract
MicroRNA-based therapies that target cardiomyocyte proliferation have great potential for the treatment of myocardial infarction (MI). In previous work, we showed that the miR-302/367 cluster regulates cardiomyocyte proliferation in the prenatal and postnatal heart. Here, we describe the development and application of an injectable hyaluronic acid (HA) hydrogel for the local and sustained delivery of miR-302 mimics to the heart. We show that the miR-302 mimics released in vitro promoted cardiomyocyte proliferation over one week, and that a single injection of the hydrogel in the mouse heart led to local and sustained cardiomyocyte proliferation for two weeks. After MI, gel/miR-302 injection caused local clonal proliferation and increased cardiomyocyte numbers in the border zone of a Confetti mouse model. Gel/miR-302 further decreased cardiac end-diastolic (39%) and end-systolic (50%) volumes, and improved ejection fraction (32%) and fractional shortening (64%) four weeks after MI and injection, compared to controls. Our findings suggest that biomaterial-based miRNA delivery systems can lead to improved outcomes in cardiac regeneration.
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Delivery of Hippo inhibiting miR302 b/c mimics stimulates cardiomyocyte proliferation and cardiac repair following MI in mice.
“For example, the delivery of Hippo inhibiting miR302 b/c mimics stimulates cardiomyocyte proliferation and cardiac repair following MI in mice34.”
From 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels (2021) · cites this paper as [34]
Recent pre-clinical evidence indicates that Hippo pathway inhibiting miRNAs can stimulate CM proliferation.
“Recent pre-clinical evidence indicates that Hippo pathway inhibiting miRNAs can stimulate CM proliferation34,57,58.”
From 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels (2021) · cites this paper as [34]
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References 56 · Cited by 239
Research works printed but not linked: 1
- [38]López CA de Vries AH Marrink SJ Molecular mechanism of cyclodextrin mediated cholesterol extraction PLoS Comput. Biol 7 e1002020 2011 21455285 PMC3063748
- Authors
- Wang, L. L., Liu, Y., Chung, J. J., Wang, T., Gaffey, A. C., Lu, M., Cavanaugh, C. A., Zhou, S., Kanade, R., Atluri, P., Morrisey, E. E., & Burdick, J. A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Morrisey, Edward E.
- Burdick, Jason A.
- ORCID
- Venue
- Nature Biomedical Engineering
- Published
- 2017-11-27
- Volume
- 1
- Issue
- 12
- Pages
- 983-992
- ISSN
- 2157-846X (ISSN-L)
- PMC
- PMC5773070
- OpenAlex
- W2769590605
- Cited by
- 239
- References
- 56
- Citations by year
- 2026: 12 · 2025: 29 · 2024: 24 · 2023: 28 · 2022: 25 · 2021: 37 · 2020: 36 · 2019: 25 · 2018: 20 · 2017: 3
- FWCI
- 9.38
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- Nature Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U01HL134745, U01HL100405, F30HL134255, R01HL135090)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- microRNA delivery, hyaluronic acid hydrogel, miR-302/367 cluster, cardiomyocyte proliferation, myocardial infarction, cardiac regeneration, injectable biomaterials, sustained drug release, cardiac function
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