Abstract
Mesenchymal stromal/stem cell (MSC)-based therapy is a promising approach for the treatment of heart failure. However, current MSC-delivery methods result in poor donor cell engraftment, limiting the therapeutic efficacy. To address this issue, we introduce here a novel technique, epicardial placement of bi-layered, adhesive dressings incorporating MSCs (MSC-dressing), which can be easily fabricated from a fibrin sealant film and MSC suspension at the site of treatment. The inner layer of the MSC dressing, an MSC-fibrin complex, promptly and firmly adheres to the heart surface without sutures or extra glues. We revealed that fibrin improves the potential of integrated MSCs through amplifying their tissue-repair abilities and activating the Akt/PI3K self-protection pathway. Outer collagen-sheets protect the MSC-fibrin complex from abrasion by surrounding tissues and also facilitates easy handling. As such, the MSC-dressing technique not only improves initial retention and subsequent maintenance of donor MSCs but also augment MSC's reparative functions. As a result, this technique results in enhanced cardiac function recovery with improved myocardial tissue repair in a rat ischemic cardiomyopathy model, compared to the current method. Dose-dependent therapeutic effects by this therapy is also exhibited. This user-friendly, highly-effective bioengineering technique will contribute to future success of MSC-based therapy.
Highlights
Mesenchymal stromal/stem cells (MSCs) have a potential to treat diseases that are difficult to cure with existing treatments, including severe heart failure [1,2]
Japan) is a self-assembling peptide hydrogel developed for hemostasis [24], and we have reported that epicardial placement of an instantly produced PuraMatrix®-MSC complex resulted in increased donor cell survival and enhanced therapeutic effects, compared to IM injection, in rat heart failure models [15]
We have demonstrated that epicardial placement of a complex of MSCs and fibrin glue, which is currently used for hemostasis during surgery, improved donor cell engraftment and augmented therapeutic outcome, compared to IM injection, in a rodent model [16]
Summary
Mesenchymal stromal/stem cells (MSCs) have a potential to treat diseases that are difficult to cure with existing treatments, including severe heart failure [1,2]. A range of cardiac patch products have been reported in translational studies [21,22,23], among which skeletal myoblast-sheets [19] and pre-fabricated fibrin glue patch-incorporating cardiac progenitor cells [20] have already been applied to heart failure patients These methods based on pre-fabricated bio-products are associated with limited availability due to highly-specialized cell culture steps in a clinical-grade cell processing facility, demanding quality control and complicated logistics. These products require sutures or additional glue to stabilize them on the heart surface. Glues may form an unwanted gap between the cardiac patch and epicardium, inhibiting the permeation of MSC's secretome into the myocardium, which will limit the paracrine effect
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