Minimally invasive delivery of therapeutic agents by hydrogel injection into the pericardial cavity for cardiac repair
Top Cited Papers
Open Access
- 3 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-10
- https://doi.org/10.1038/s41467-021-21682-7
Abstract
Cardiac patches are an effective way to deliver therapeutics to the heart. However, such procedures are normally invasive and difficult to perform. Here, we develop and test a method to utilize the pericardial cavity as a natural “mold” for in situ cardiac patch formation after intrapericardial injection of therapeutics in biocompatible hydrogels. In rodent models of myocardial infarction, we demonstrate that intrapericardial injection is an effective and safe method to deliver hydrogels containing induced pluripotent stem cells-derived cardiac progenitor cells or mesenchymal stem cells-derived exosomes. After injection, the hydrogels form a cardiac patch-like structure in the pericardial cavity, mitigating immune response and increasing the cardiac retention of the therapeutics. With robust cardiovascular repair and stimulation of epicardium-derived cells, the delivered therapeutics mitigate cardiac remodeling and improve cardiac functions post myocardial infarction. Furthermore, we demonstrate the feasibility of minimally-invasive intrapericardial injection in a clinically-relevant porcine model. Collectively, our study establishes intrapericardial injection as a safe and effective method to deliver therapeutic-bearing hydrogels to the heart for cardiac repair.Funding Information
- American Heart Association (18TPA34230092, 19EIA34660286)
- National Institutes of Health
This publication has 66 references indexed in Scilit:
- Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial InfarctionScience Translational Medicine, 2013
- Transplantation of platelet gel spiked with cardiosphere-derived cells boosts structural and functional benefits relative to gel transplantation alone in rats with myocardial infarctionBiomaterials, 2012
- Catheter-Deliverable Hydrogel Derived From Decellularized Ventricular Extracellular Matrix Increases Endogenous Cardiomyocytes and Preserves Cardiac Function Post-Myocardial InfarctionJournal of the American College of Cardiology, 2012
- Exosomes From Human CD34 + Stem Cells Mediate Their Proangiogenic Paracrine ActivityCirculation Research, 2011
- Harnessing the potential of induced pluripotent stem cells for regenerative medicineNature, 2011
- Delivery of gelfoam-enabled cells and vectors into the pericardial space using a percutaneous approach in a porcine modelGene Therapy, 2011
- Composite scaffold provides a cell delivery platform for cardiovascular repairProceedings of the National Academy of Sciences of the United States of America, 2011
- Developmental and Regenerative Biology of Multipotent Cardiovascular Progenitor CellsCirculation Research, 2011
- Intrapericardial triamcinolone for acute pericarditis after electrophysiologic proceduresAmerican Journal of Health-System Pharmacy, 2010
- Naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineeringBiomaterials, 2009