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Engineered mesenchymal cell-based patches as controlled VEGF delivery systems to induce extrinsic angiogenesis

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Boccardo Stefano, Gaudiello Emanuele, Melly Ludovic, Cerino Giulia, Ricci Davide, Martin Ivan, Eckstein Friedrich, Banfi Andrea, Marsano Anna,
Project Engineering of a cell-loaded patch as a controlled VEGF-releasing device to treat cardiac ischemia
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Original article (peer-reviewed)

Journal Acta Biomaterialia
Volume (Issue) 42
Page(s) 127 - 135
Title of proceedings Acta Biomaterialia
DOI 10.1016/j.actbio.2016.07.041.

Open Access

Abstract

Therapeutic over-expression of Vascular Endothelial Growth Factor (VEGF) by transduced progenitors is a promising strategy to efficiently induce angiogenesis in ischemic tissues (e.g. limb muscle and myocardium), but tight control over the micro-environmental distribution of the dose is required to avoid induction of angioma-like tumors. Therapeutic VEGF release was achieved by purified transduced adipose mesenchymal stromal cells (ASC) that homogeneously produce specific VEGF levels, inducing only normal angiogenesis after injection in non-ischemic tissues. However, the therapeutic potential of this approach mostly in the cardiac field is limited by the poor cell survival and the restricted area of effect confined to the cell-injection site. The implantation of cells previously organized in vitro in 3D engineered tissues could overcome these issues. Here we hypothesized that collagen sponge-based construct (patch), generated by ASC expressing controlled VEGF levels, can function as delivery device to induce angiogenesis in surrounding areas (extrinsic vascularization). A 7-mm-thick acellular collagen scaffold (empty), sutured beneath the patch, provided a controlled and reproducible model to clearly investigate the ongoing angiogenesis in subcutaneous mice pockets. VEGF-expressing ASC significantly increased the capillary in-growth inside both the patch itself and the empty scaffold compared to naïve cells, leading to significantly improved survival of implanted cells. These data suggest that this strategy confers control (i) on angiogenesis efficacy and safety by means of ASC expressing therapeutic VEGF levels and (ii) over the treated area through the specific localization in an engineered collagen sponge-based patch.
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