Journal
NATURE BIOMEDICAL ENGINEERING
Volume 1, Issue 12, Pages 983-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41551-017-0157-y
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Funding
- American Heart Association
- National Institutes of Health [F30 HL134255, UO1 HL100405, U01 HL134745]
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MicroRNA-based therapies that target cardiomyocyte proliferation have great potential for the treatment of myocardial infarction. 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 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 myocardial infarction, 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 myocardial infarction and injection, compared with controls. Our findings suggest that biomaterial-based miRNA delivery systems can lead to improved outcomes via cardiac regeneration after myocardial infarction.
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