On-site fabrication of Bi-layered adhesive mesenchymal stromal cell-dressings for the treatment of heart failure

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.

Human amnion-derived mesenchymal stem cells attenuate xenogeneic graft-versus-host disease by preventing T cell activation and proliferation

“…Human AMSC were generated as previously described 12 . Amniotic membranes procured following cesarean section of pregnant females were treated with collagenase and dispase (Sigma Aldrich, MO, USA) 10 , 12 . Human BMSC from healthy donors were purchased from AllCells (CA, USA).…”

“…Additionally, the immunomodulatory characteristics of mesenchymal cells within fetal membranes play key roles in fetal-maternal tolerance 9 . Several recent studies reported that human amnion-derived MSC (AMSC) exhibited therapeutic efficacy in rodent disease models including colitis induced by chemicals 10 , 11 , heart failure induced by coronary artery ligation 12 , and allo-GVHD 13 .…”

Multifaceted Design and Emerging Applications of Tissue Adhesives

“…This work showed that the adhesive matrix can promote MSCs’ function and the technique enhanced cardiac function recovery with improved myocardial tissue repair in a rat ischemic cardiomyopathy model. [ 351 ]…”

Scaffold-free cell-based tissue engineering therapies: advances, shortfalls and forecast

“…Traditional scaffold-based tissue engineering strategies employ a cytocompatible, biodegradable and mechanically stable natural or synthetic in origin polymeric scaffold with a fully interconnected porous network for efficient transport and exchange of oxygen, nutrients and metabolites 13 , 14 . Although very many scaffold conformations (e.g., hydrogels 15 , 16 , sponges 17 , 18 , fibres 19 , 20 , films 21 , 22 ) have been developed, and have demonstrated safety and efficacy in preclinical setting and phase I clinical trials as cell delivery vehicles, only a handful of them constitute a Food and Drug Administration (FDA)/European Medicines Agency (EMA) approved device (Table 1 ). This limited technology transfer from laboratory benchtop to clinical applicability has been attributed to component (e.g., limited understanding of the mechanism of action of the various device components; device components do not comply with regulatory frameworks; toxicity issues) and process (e.g., too complex to allow for large-scale efficient and reproducible manufacturing; too long to be profitable) limitations.…”