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.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Feb 2014|
Bibliographical noteFunding Information:
Financial support for this research was provided by the National Institutes of Biomedical Imaging and Bioengineering (NIBIB) at the National Institutes of Health (NIH) through grant number R01 EB009910 , R01 EB005678 , and R01 CA173745 . This work was also supported by the Northwestern University RHLCCC Flow Cytometry Facility and a Cancer Center Support Grant ( NCI CA060553 ).
- Flow cytometry
- Gene therapy