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

Biomaterials. 2019 Jul;209:41-53. doi: 10.1016/j.biomaterials.2019.04.014. Epub 2019 Apr 16.

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.

Keywords: Bioengineering; Cardiac patch; Fibrin sealant film; Mesenchymal stromal cell; Myocardial repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bioengineering / methods
  • Blotting, Western
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / pathology
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Heart Failure / therapy*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Myocardium / cytology
  • Myocardium / metabolism
  • Pregnancy
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Scaffolds

Substances

  • Hydrogen Peroxide