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dc.contributor.authorDash, Biraja C.
dc.contributor.authorThomas, Dilip
dc.contributor.authorMonaghan, Michael
dc.contributor.authorCarroll, Oliver
dc.contributor.authorChen, Xizhe
dc.contributor.authorWoodhouse, Kimberly
dc.contributor.authorO'Brien, Timothy
dc.contributor.authorPandit, Abhay
dc.date.accessioned2016-03-22T16:15:51Z
dc.date.issued2015-10
dc.identifier.citationDash, BC,Thomas, D,Monaghan, M,Carroll, O,Chen, XZ,Woodhouse, K,O'Brien, T,Pandit, A (2015) 'An injectable elastin-based gene delivery platform for dose-dependent modulation of angiogenesis and inflammation for critical limb ischemia'. Biomaterials, 65 :126-139.en_IE
dc.identifier.issn1878-5905
dc.identifier.urihttp://hdl.handle.net/10379/5625
dc.description.abstractCritical limb ischemia is a major clinical problem. Despite rigorous treatment regimes, there has been only modest success in reducing the rate of amputations in affected patients. Reduced level of blood flow and enhanced inflammation are the two major pathophysiological changes that occur in the ischemic tissue. The objective of this study was to develop a controlled dual gene delivery system capable of delivering therapeutic plasmid eNOS and IL-10 in a temporal manner. In order to deliver multiple therapeutic genes, an elastin-like polypeptide (ELP) based injectable system was designed. The injectable system was comprised of hollow spheres and an in situ-forming gel scaffold of elastin-like polypeptide capable of carrying gene complexes, with an extended manner release profile. In addition, the ELP based injectable system was used to deliver human eNOS and IL-10 therapeutic genes in vivo. A subcutaneous dose response study showed enhanced blood vessel density in the treatment groups of eNOS (20 rig) and IL-10 (10 mu g)/eNOS (20 mu g) and reduced inflammation with IL-10 (10 mu g) alone. Next, we carried out a hind-limb ischemia model comparing the efficacy of the following interventions; Saline; IL-10, eNOS and IL-10/eNOS. The selected dose of eNOS, exhibited enhanced angiogenesis. IL-10 treatment groups showed reduction in the level of inflammatory cells. Furthermore, we demonstrated that eNOS up-regulated major proangiogenic growth factors such as vascular endothelial growth factors, platelet derived growth factor B, and fibroblast growth factor 1, which may explain the mechanism of this approach. These factors help in formation of a stable vascular network. Thus, ELF injectable system mediating non-viral delivery of human IL10-eNOS is a promising therapy towards treating limb ischemia. (C) 2015 Elsevier Ltd. All rights reserved.en_IE
dc.description.sponsorshipScience Foundation Ireland grant no. 07/SRC/B1163en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherElsevieren_IE
dc.relation.ispartofBiomaterialsen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectElastin-like polypeptideen_IE
dc.subjectHollow spheresen_IE
dc.subjectCritical limb ischemiaen_IE
dc.subjectGene therapyen_IE
dc.subjectAngiogenesisen_IE
dc.subjectInflammationen_IE
dc.subjectPDGF-BBen_IE
dc.subjectPeripheral arterial diseaseen_IE
dc.subjectHindlimb ischemiaen_IE
dc.subjectEndogenous inhibitorsen_IE
dc.subjectHuman monocytesen_IE
dc.subjectNitric oxideen_IE
dc.subjectStem cellsen_IE
dc.subjectTherapyen_IE
dc.subjectAciden_IE
dc.subjectInterleukin-10en_IE
dc.titleAn injectable elastin-based gene delivery platform for dose-dependent modulation of angiogenesis and inflammation for critical limb ischemiaen_IE
dc.typeArticleen_IE
dc.date.updated2015-12-30T17:58:04Z
dc.identifier.doi10.1016/j.biomaterials.2015.06.037
dc.local.publishedsourcehttp://www.sciencedirect.com/science/article/pii/S0142961215005517en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|
dc.description.embargo2017-10-31
dc.internal.rssid9400727
dc.local.contactAbhay Shashikant Pandit, Curam, Biosciences, Nui Galway. 2758 Email: abhay.pandit@oegaillimh.ie
dc.local.copyrightcheckedNo
dc.local.versionPUBLISHED
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Ireland