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.
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Gower
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Boehler
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Samira M
authors.initials: SM
authors.lastname: Azarin
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Christine F
authors.initials: CF
authors.lastname: Ricci
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA; Chemistry of Life Processes Institute (CLP), Northwestern University, Evanston, IL, USA.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Leonard
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA; Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA; Institute for BioNanotechnology in Medicine (IBNAM), Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA; Chemistry of Life Processes Institute (CLP), Northwestern University, Evanston, IL, USA. Electronic address: l-shea@northwestern.edu.
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D056747:Immunomodulation / Q000502:physiology; D016753:Interleukin-10 / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D016753:Interleukin-10
keywords: Flow cytometry; Gene therapy; Immunomodulation; Inflammation; Leukocyte; Scaffold