Journal
BIOMATERIALS
Volume 154, Issue -, Pages 12-23Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.10.050
Keywords
Self-assembling peptide hydrogel; Bioengineering; Mesenchymal stromal cell; Cell transplantation therapy; Heart failure
Funding
- British Heart Foundation [RG/15/3/31236]
- Heart Research UK (Translational Research Grant) [RG2618/12/13]
- NIHR Barts Biomedical Research Centre
- Kaneka Corp.
- 3-D Matrix Ltd.
- British Heart Foundation [PG/12/10/29389] Funding Source: researchfish
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Transplantation of mesenchymal stromal cells (MSCs) is an emerging therapy for the treatment of heart failure. However, the delivery method of MSC is currently suboptimal. The use of self-assembling peptide hydrogels, including PuraMatrix (R) (PM; 3-D Matrix, Ltd), has been reported for clinical hemostasis and in research models. This study demonstrates the feasibility and efficacy of an advanced approach for MSC-therapy, that is coating of the epicardium with the instantly-produced PM hydrogel incorporating MSCs (epicardial PM-MSC therapy). We optimized the conditions/procedure to produce instant 2PM-MSC complexes. After spreading on the epicardium by easy pipetting, the PM-MSC complex promptly and stably adhere to the beating heart. Of note, this treatment achieved more extensive improvement of cardiac function, with greater initial retention and survival of donor MSCs, compared to intramyocardial MSC injection in rat heart failure models. This enhanced efficacy was underpinned by amplified myocardial upregulation of a group of tissue repair-related genes, which led to enhanced repair of the damaged myocardium, i.e. augmented microvascular formation and reduced interstitial fibrosis. These data suggest a potential for epicardial PM-MSC therapy to be a widely-adopted treatment of heart failure. This approach may also be useful for treating diseases in other organs than the heart. (c) 2017 The Authors. Published by Elsevier Ltd.
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