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Published on: November 26, 2018
Characterization of decellularized left and right ventricular myocardial matrix hydrogels and their effects on
Jervaughn D Hunter1, Arielle Hancko1, Preety Shakya2
1Department of Bioengineering, Sanford Consortium for Regenerative Medicine, UC San Diego, USA.
Insights
This study explored extracellular matrix hydrogels for treating pediatric right heart failure. Myocardial matrix hydrogels protected cardiac progenitor cells during delivery and enhanced their signaling, showing promise for regenerative therapy.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Cardiovascular Research
Background:
- Congenital heart defects are the primary cause of pediatric right heart failure.
- Current cardiac progenitor cell (CPC) therapy for right ventricular (RV) failure faces challenges with cell survival, engraftment, and retention.
- Delivery methods and the hostile RV microenvironment (e.g., reactive oxygen species) limit therapeutic efficacy.
Purpose of the Study:
- To characterize left ventricular (LV) and RV myocardial matrix (MM) hydrogels.
- To evaluate their potential as delivery vehicles for CPCs in treating RV failure.
- To assess hydrogel-enhanced CPC protection against injection forces and reactive oxygen species (ROS), and to evaluate their angiogenic paracrine signaling.
Main Methods:
- Characterization of LV and RV MM hydrogels.
- In vitro assessment of CPCs encapsulated in LV MM and RV MM.
- Evaluation of hydrogel protection against needle forces and ROS.
- Analysis of angiogenic paracrine signaling by encapsulated CPCs and MM alone.
Main Results:
- LV and RV MM hydrogels exhibit similar physical properties but distinct protein signatures.
- Both LV MM and RV MM equally protected CPCs against needle forces and ROS.
- CPCs in both LV MM and RV MM showed enhanced angiogenic paracrine signaling compared to CPCs in collagen.
- RV MM alone improved vascular tube formation, indicating potential as a standalone therapy.
Conclusions:
- Injectable LV and RV MM hydrogels are effective in protecting CPCs during delivery and enhancing their therapeutic potential for RV failure.
- The RV MM hydrogel shows promise as both a cell delivery vehicle and a standalone therapeutic agent.
- Further investigation into MM hydrogels for RV failure treatment is warranted.
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.
