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EXAMINING THE ROLE OF MACROPHAGES IN PROLIFERATING INFANTILE HEMANGIOMAS
Presenter: Alvin Wong
Co-Authors: Hardy K; England R; Shawber CJ; Kitajewski J; Wu JK
Columbia University

Background: Infantile hemangiomas (IH) are a common benign endothelial cell tumor thought to be of stem cell origin (HemSC). Histological analysis indicates that IH consist of endothelial cells (HemEC) and associated macrophages. A role for macrophages in IH progression has been postulated (Ref 1), though their function has yet to be characterized. Our study investigates macrophages in hemangioma development using a murine IH model. This model can eventually be used to study the origin and function of IH-associated macrophages.

Materials and Methods: HemSCs were isolated from resected IH tissues via CD 133+ magnetic bead selection. CD133+ cells were re-suspended in matrigel and implanted subcutaneously into immunodeficient mice. At weeks 2 and 3, the mice were sacrificed and the implant removed for histologic analyses. The IH implants were evaluated and compared with clinically resected patient IH tissues. Specific antibodies for murine and human macrophages were used for immunohistochemistry.

Results: Clusters of macrophages stained positive for the human-specific macrophage antibody CD68 in the space surrounding the vessel structures of clinical IH specimens (Fig 1). The CD133+/CD31- HemSCs in the IH implants differentiated into CD31+/Glut1+ vessels and adipocytes in the matrigel. In IH implants, numerous F4/80 positive macrophages derived from the host surrounded the HemECs with a phenotype similar to that observed in the clinical specimens (Fig 2).

Conclusion: Our study demonstrated successful differentiation of HemSCs into CD31+/Glut1+ endothelial cells in the IH murine model. The presence of murine macrophages was found in association with HemECs and suggests that these cells may contribute to the differentiation of HemSCs into endothelial cells. These myeloid derived cells are not an intrinsic component of infantile hemangiomas (Ref 1), but are recruited to the abnormal HemECs. Further studies are being conducted to characterize the relationship and signaling between HemSCs and macrophages.References1. Ritter, M.R. et al. (2006). Myeloid Cells in Infantile Hemangioma. Am J Pathol., 168(2), 621-628


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