Characterization of decellularized left and right ventricular myocardial matrix hydrogels and their effects on cardiac progenitor cells. (October 2022)

• Record Type: Journal Article
• Authors: Hunter, Jervaughn D.; Hancko, Arielle; Shakya, Preety; Hill, Ryan; Saviola, Anthony J.; Hansen, Kirk C.; Davis, Michael E.; Christman, Karen L.
• Is Part Of: Journal of molecular and cellular cardiology. Volume 171(2022)
• Page Start: 45
• Page End: 55
• Publication Date: 2022-10
• Subjects: Right ventricle -- left ventricle -- cardiac progenitor cells -- extracellular matrix -- biomaterial -- hydrogel; bFGF basic fibroblast growth factor -- CEC cardiac endothelial cell -- CHD congenital heart disease -- CPCs c-kit+ cardiac progenitor cells -- ECM extracellular matrix -- EF ejection fraction -- FBS fetal bovine serum -- HF heart failure -- ITS Insulin-Transferrin-Selenium -- LV left ventricle -- MI myocardial infarction -- MM myocardial matrix -- PAB pulmonary artery banded -- PAGE polyacrylamide gel electrophoresis -- PBS phosphate buffered saline -- ROS reactive oxygen species -- RV right ventricle -- SEM scanning electron microscopy -- SDS sodium dodecyl sulfate -- sGAG sulfated glycosaminoglycan; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2022.06.007
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Congenital heart defects are the leading cause of right heart failure in pediatric patients. Implantation of c-kit + cardiac-derived progenitor cells (CPCs) is being clinically evaluated to treat the failing right ventricle (RV), but faces limitations due to reduced transplant cell survival, low engraftment rates, and low retention. These limitations have been exacerbated due to the nature of cell delivery (narrow needles) and the non-optimal recipient microenvironment (reactive oxygen species (ROS)). Extracellular matrix (ECM) hydrogels derived from porcine left ventricular (LV) myocardium have emerged as a potential therapy to treat the ischemic LV and have shown promise as a vehicle to deliver cells to injured myocardium. However, no studies have evaluated the combination of an injectable biomaterial, such as an ECM hydrogel, in combination with cell therapy for treating RV failure. In this study we characterized LV and RV myocardial matrix (MM) hydrogels and performed in vitro evaluations of their potential to enhance CPC delivery, including resistance to forces experienced during injection and exposure to ROS, as well as their potential to enhance angiogenic paracrine signaling. While physical properties of the two hydrogels are similar, the decellularized LV and RV have distinct protein signatures. Both materials were equally effective in protecting CPCs against needle forces and ROS. CPCs encapsulated in either the LV MM or RV MM exhibited similar enhanced potential for angiogenic paracrine signaling when compared to CPCs in collagen. The RV MM without cells, however, likewise improved tube formation, suggesting it should also be evaluated as a potential standalone treatment. Graphical abstract: Unlabelled Image Highlights: Decellularized RV and LV ECM have distinct protein compositions. LV and RV MM hydrogels protected CPCs from forces due to needle injection and ROS. LV MM and RV MM enhanced angiogenic properties of CPCs over CPCs in collagen. RV MM alone induced significant tube formation, warranting further study of RV MM.