(680g) Induced M2 Macrophage Activation by IL10 Virus Delivery

Boehler, R. M. - Presenter, Northwestern University
Shin, S. - Presenter, Northwestern University
Leonard, J. N. - Presenter, Northwestern University
Shea, L. D. - Presenter, Northwestern University
Goodman, A. - Presenter, Northwestern University
Pilecki, M. - Presenter, Northwestern University

The ability of injured tissue to functionally regenerate as opposed to developing into non-functional scar tissue is drastically impacted by the host response following injury. Many tissue engineering approaches involve the implantation of biomaterials and/or delivery of therapeutic factors. Thus, inflammation results from additive responses to the injury, the biomaterial, and the factors that are being delivered. Excessive inflammation can inhibit the regeneration of tissues such as spinal cord, where activated macrophages create an environment that induces cell death and matrix remodeling. Macrophage activation state may influence the extent of tissue regeneration. M1 (classical) activation is characterized by production of pro-inflammatory cytokines and toxic reactive oxygen species whereas M2 activation induces anti-inflammatory responses, debris scavenging, angiogenesis, and tissue repair. Preliminary immunohistochemistry results with our materials indicate an M1 environment after injury as evidenced by oxidative activity, cell death, and a lack of M2 macrophages in the injury site, and we are investigating gene delivery as a mechanism to switch the phenotype and thereby create an anti-inflammatory microenvironment. Gene delivery from biomaterials results in transgene expression by macrophages, which provides an opportunity to modulate macrophage function and the course of inflammation. Lentiviral delivery results in expression that persists above background levels for at least four weeks, which is consistent with the timing over which macrophages are present. A viral vector encoding IL-10 was delivered to reduce inflammation and switch the macrophage to the regenerative M2 phenotype rather than the inflammatory M1. IL-10 virus delivery results in an upregulation of the anti-inflammatory macrophage surface marker CD163 by analytical flow cytometry at one week, suggesting an increase in M2 macrophages. This study provides a step towards controlling the inflammatory response to implanted biomaterials and presents the opportunity to enhance nerve regeneration following spinal cord injury by viral IL-10 delivery.