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

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 placeme...

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Bibliographic Details
Published in:Biomaterials 2019-07, Vol.209, p.41-53
Main Authors: Kobayashi, Kazuya, Ichihara, Yuki, Sato, Nobuhiko, Umeda, Nobuyoshi, Fields, Laura, Fukumitsu, Masafumi, Tago, Yoshiyuki, Ito, Tomoya, Kainuma, Satoshi, Podaru, Mihai, Lewis-McDougall, Fiona, Yamahara, Kenichi, Uppal, Rakesh, Suzuki, Ken
Format: Article
Language:English
Subjects:
Animals
Bioengineering
Bioengineering - methods
Blotting, Western
Cardiac patch
Cardiomyopathies - metabolism
Cardiomyopathies - pathology
Cells, Cultured
Female
Fibrin sealant film
Flow Cytometry
Heart Failure - therapy
Humans
Hydrogen Peroxide - pharmacology
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - drug effects
Mesenchymal stromal cell
Myocardial repair
Myocardium - cytology
Myocardium - metabolism
Pregnancy
Rats
Reverse Transcriptase Polymerase Chain Reaction
Tissue Scaffolds
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2019.04.014