Abstract
Transplantation of mesenchymal stromal cells (MSCs) is a promising new therapy for heart failure. However, the current cell delivery routes result in poor donor cell engraftment. We therefore explored the role of fibrin glue (FG)-aided, instant epicardial placement to enhance the efficacy of MSC-based therapy in a rat ischemic cardiomyopathy model. We identified a feasible and reproducible method to instantly produce a FG-MSC complex directly on the heart surface. This complex exhibited prompt, firm adhesion to the heart, markedly improving initial retention of donor MSCs compared to intramyocardial injection. In addition, maintenance of retained MSCs was enhanced using this method, together contributing the increased donor cell presence. Such increased donor cell quantity using the FG-aided technique led to further improved cardiac function in association with augmented histological myocardial repair, which correlated with upregulation of tissue repair-related genes. We identified that the epicardial layer was eliminated shortly after FG-aided epicardial placement of MSCs, facilitating permeation of the donor MSC’s secretome into the myocardium enabling myocardial repair. These data indicate that FG-aided, on-site, instant epicardial placement enhances MSC engraftment, promoting the efficacy of MSC-based therapy for heart failure. Further development of this accessible, advanced MSC-therapy is justified.
Highlights
Engraftment of donor mesenchymal stromal cells (MSCs) resulted in amplified myocardial repair and augmented cardiac function recovery
Fibrin glues (FG)-aided, instant epicardial placement markedly improved both initial retention and survival of donor MSCs compared to IM injection
Thereafter, donor cell presence was reduced in both groups; throughout the time course up to day 28, greater donor MSC presence was consistently observed in the FG-MSC group
Summary
Engraftment of donor MSCs resulted in amplified myocardial repair and augmented cardiac function recovery. As FG can serve as a suitable three-dimensional scaffold for cultured cells, this biomaterial has been widely used as a cell culture system, a component of tissue engineering constructs or as an injectable material mixed with cells[12] The capabilities of this biomaterial to enhance therapeutic effects of cell transplantation therapy have been increasingly recognized in various diseases in bone, cartilage, cornea, blood vessel, tendon and heart[12]. By delivering ready-to-use, quality-controlled MSCs together with the safety-proven fibrinogen and thrombin solutions, logistics and quality control of this product is straightforward, without the requirement for a cell processing facility in each hospital This user-friendly technique has a great potential to become a widely adopted MSC-based therapy for heart failure. We aimed to uncover the mechanistic factors underpinning the role of FG to achieve effective epicardial placement of MSCs for the treatment of heart failure
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