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Examining the Role of Macrophages in Proliferating Infantile Hemangiomas
Diya Banerjee, BA, Krista Hardy, BS, Alvin Wong, MD, Ryan England, BS, Carrie J. Shawber, PhD, Jan K. Kitajewski, PhD, June K. Wu, MD.
Columbia University, New York, NY, USA.

PURPOSE:
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(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.
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 in the space surrounding IH vessel structures stained positive for human specific macrophage antibodies CD 68 and CD 163 (Fig 1). In the in vivo murine model, HemSCs formed vessel structures surrounded by numerous macrophages. These macrophages stained positive for mouse specific F4/80 and MOMA-2 confirming that they were derived from the host. The IH implant demonstrated a macrophage phenotype similar to that observed in the clinical specimens.
CONCLUSION:
Our study demonstrated successful differentiation of HemSCs into vascular structures in the IH murine model. The presence of murine macrophages was found in association with these vessels 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, but are recruited to the abnormal HemECs. Further studies are being conducted to characterize the relationship and signaling between HemSCs and macrophages.
References
1. Ritter, M.R. et al. (2006). Myeloid Cells in Infantile Hemangioma. Am J Pathol., 168(2), 621-628


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