Journal
BIOMATERIALS
Volume 291, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121877
Keywords
Cardiac repair; Extracellular vesicles; Heart failure; Injectable biomaterial; Mesenchymal stromal cells; Myocardial ischemia-reperfusion
Funding
- INSERM
- Agence Nationale de la Recherche [ANR-17-CE18-0003-01, ANR-17-CE18-0003-04]
- Assistance Publique-Hopitaux de Paris
- Universite Paris Cite
- Agence Nationale de la Recherche (ANR) [ANR-17-CE18-0003] Funding Source: Agence Nationale de la Recherche (ANR)
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Loading extracellular vesicles (EV) into hyaluronic acid (HA) biomaterial improves their delivery in the failing myocardium, preserving cardiac function, promoting angiogenesis, and reducing apoptosis and fibrosis.
Extracellular vesicles (EV) are increasingly recognized as a therapeutic option in heart failure. They are usually administered by direct intramyocardial injections with the caveat of a rapid wash-out from the myocardium which might weaken their therapeutic efficacy. To improve their delivery in the failing myocardium, we designed a system consisting of loading EV into a clinical-grade hyaluronic acid (HA) biomaterial. EV were isolated from umbilical cord-derived mesenchymal stromal cells. The suitability of HA as a delivery platform was then assessed in vitro. Rheology studies demonstrated the viscoelastic and shear thinning behaviors of the selected HA allowing its easy injection. Moreover, the release of HA-embedded EV was sustained over more than 10 days, and EV bioactivity was not altered by the biomaterial. In a rat model of myocardial ischemia reperfusion, we showed that HA-embedded EV preserved cardiac function (echocardiography), improved angiogenesis and decreased both apoptosis and fibrosis (histology and transcriptomics) when compared to intramyocardial administration of EV alone. These data thus strengthen the concept that inclusion of EV into a clinically useable biomaterial might opti-mize their beneficial effects on post-ischemic cardiac repair.
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