Localized temporal co-delivery of interleukin 10 and decorin genes using amediated by collagen-based biphasic scaffold modulates the expression of TGF-β1/β2 in a rabbit ear hypertrophic scarring model
Hypertrophic scarring (HS) is an intractable complication associated with cutaneous wound healing. Although transforming growth factor β1 (TGF-β1) has long been documented as a central regulatory cytokine in fibrogenesis and fibroplasia, there is currently no cure. Gene therapy is emerging as a powe...
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Published in | Biomaterials science Vol. 9; no. 8; pp. 3136 - 3149 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
Royal Society of Chemistry
21.04.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Hypertrophic scarring (HS) is an intractable complication associated with cutaneous wound healing. Although transforming growth factor β1 (TGF-β1) has long been documented as a central regulatory cytokine in fibrogenesis and fibroplasia, there is currently no cure. Gene therapy is emerging as a powerful tool to attenuate the overexpression of TGF-β1 and its signaling activities. An effective approach may require transferring multiple genes to regulate different aspects of TGF-β1 signaling activities in a Spatio-temporal manner. Herein we report the additive anti-fibrotic effects of two plasmid DNAs encoding interleukin 10 (IL-10) and decorin (DCN) co-delivered
via
a biphasic 3D collagen scaffold reservoir platform. Combined gene therapy significantly attenuated inflammation and extracellular matrix components' accumulation in a rabbit ear ulcer model; and suppressed the expressions of genes associated with fibrogenesis, including collagen type I, as well as TGF-β1 and TGF-β2, while enhancing the genes commonly associated with regenerative healing including collagen type III. These findings may serve to provide a non-viral gene therapy platform that is safe, optimized, and effective to deliver multiple genes onto the diseased tissue in a wider range of tissue fibrosis-related maladies.
The study shows that although pIL-10/pDCN therapy are individually able to suppress TGF-β1/β2, only the combined overexpression of both transgenes was efficacious in suppressing TGF-β1/β2 and concurrently sustaining the upregulation of TGF-β3. |
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Bibliography: | 10.1039/d0bm01928c Electronic supplementary information (ESI) available. See DOI ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2047-4830 2047-4849 |
DOI: | 10.1039/d0bm01928c |