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

Kazuya Kobayashi, Yuki Ichihara, Nobuhiko Sato, Nobuyoshi Umeda, Laura Fields, Masafumi Fukumitsu, Yoshiyuki Tago, Tomoya Ito, Satoshi Kainuma, Mihai Podaru, Fiona Lewis-McDougall, Kenichi Yamahara, Rakesh Uppal, Ken Suzuki
Biomaterials2019
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 dres- sings 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.
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