Abstract 274: Polarization of Macrophage Confers Regenerative Capacity of Using Adipose Derived Regenerative Cells

Abstract

Background: Recent studies indicate that macrophages (Mφ) have conflicting characteristics, pro-inflammatory or anti-inflammatory phenotypes. We previously demonstrated that implantation of adipose derived regenerative cells (ADRCs) augmented angiogenesis and lymph angiogenesis by modulating Mφ phenotype in animal models. We thus examine whether Mφ polarization to M2 type is important for neovascularization in various models. Methods and Results: Culture medium of ADRCs accelerated not only migration of human umbilical vein endothelial cells (HUVECs) but also polarization of M2 type Mφ. Cultured ADRCs released SDF-1, VEGF-C, and prostaglandin E2 (PGE2). PGE2 plays a key role for the polarization of M2 type Mφ via EP2/4 receptors. Matrigel tube formation assay conformed that ADRCs were incorporated into HUVEC network. In vivo, implanted ADRCs participated in the formation of capillary networks in ischemic tissue. In a mice model of tail lymphedema, the number of bone marrow derived Mφ was significantly higher in the ADRCs treated group than in the un-treated group. Most of Mφ differentiated into lymphatic endothelial cell in the edematous tissue and were polarized to M2 phenotype. Moreover, in a mice model of hind limb ischemia, implantation of ADRCs facilitated the polarization of Mφ into M2 type Mφ and up regulated IL-10 expression to suppress inflammation at ischemic tissue. Conclusion: Polarization into anti-inflammatory phenotype of Mφ plays an important role for regenerative action of ADRCs.