Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor

Zia Khan

Abstract

Infantile hemangioma (IH) is the most common vascular tumour of infancy. IH undergoes a unique life cycle consisting of robust endothelial cell proliferation and vessel formation in the proliferating phase, followed by spontaneous regression in the involuting phase. Our laboratory has shown that IH arises from multipotential stem cells termed hemangioma stem cells (HemSCs). However, the phenotype of HemSCs has not been fully elucidated. Here, I examined HemSCs and compared these lesion-derived cells to a panel of normal counterparts. My results show that HemSCs share similar gene expression profiles with human fetal liver-derived stem cells (FLSCs) and postnatal bone marrow mesenchymal/mesodermal progenitor cells (BM-MPCs). Specifically, all three precursor cell types expressed endothelial, mesenchymal, stem/progenitor, and hematopoietic lineage genes to varying degrees. Furthermore, for the first time, I show that proliferating IH lesions are immunoreactive to markers associated with hematopoiesis; namely, RUNX1, GATA2, GPR56, CD45 and CD150. However, HemSCs failed to produce hematopoietic colonies when assessed using in vitro hematopoietic activity assays. Taken together, my studies suggest that HemSCs express hematopoiesis-specific markers but their ability to undergo hematopoiesis is suppressed. Although my findings have provided greater characterization of HemSCs, more studies are needed to fully understand the mechanisms that regulate HemSC differentiation paths, and ultimately IH pathogenesis.

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