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Modulation of leukocyte infiltration and phenotype in microporous tissue engineering scaffolds via vector induced IL-10 expression

Paper ID Volume ID Publish Year Pages File Format Full-Text
6012 453 2014 8 PDF Available
Title
Modulation of leukocyte infiltration and phenotype in microporous tissue engineering scaffolds via vector induced IL-10 expression
Abstract

Biomaterial scaffolds are central to many tissue engineering strategies as they create a space for tissue growth and provide a support for cell adhesion and migration. However, biomaterial implantation results in unavoidable injury resulting in an inflammatory response, which can impair integration with the host and tissue regeneration. Toward the goal of reducing inflammation, we investigated the hypothesis that a lentiviral gene therapy-based approach to localized and sustained IL-10 expression at a scaffold could modulate the number, relative proportions, and cytokine production of infiltrating leukocyte populations. Flow cytometry was used to quantify infiltration of six leukocyte populations for 21 days following implantation of PLG scaffolds into intraperitoneal fat. Leukocytes with innate immune functions (i.e., macrophages, dendritic cells, neutrophils) were most prevalent at early time points, while T lymphocytes became prevalent by day 14. Reporter gene delivery indicated that transgene expression persisted at the scaffold for up to 28 days and macrophages were the most common leukocyte transduced, while transduced dendritic cells expressed the greatest levels of transgene. IL-10 delivery decreased leukocyte infiltration by 50% relative to controls, increased macrophage IL-10 expression, and decreased macrophage, dendritic cell, and CD4 T cell IFN-γ expression. Thus, IL-10 gene delivery significantly decreased inflammation following scaffold implant into the intraperitoneal fat, in part by modulating cytokine expression of infiltrating leukocytes.

Keywords
Inflammation; Immunomodulation; Gene therapy; Flow cytometry; Scaffold; Leukocyte
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Modulation of leukocyte infiltration and phenotype in microporous tissue engineering scaffolds via vector induced IL-10 expression
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 6, February 2014, Pages 2024–2031
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us