Loss of Thy-1 (CD90) antigen expression on mesenchymal stromal cells from hematologic malignancies is induced by in vitro angiogenic stimuli and is associated with peculiar functional and phenotypic characteristics

摘要

Background Little is known about human mesenchymal stromal cell (hMSC) phenotypic and functional subsets in response to environmental stimuli. The strategy used in this study focused on defining hMSC functional subpopulations based in particular on their Thy-1 (CD90) antigen (Ag) surface expression. Methods The effect of different in vitro microenvironmental conditions on the isolation and expansion of bone marrow-derived (BM) hMSC from hematologic malignancies (HM) and normal samples (NS) was assayed. hMSC clonogenic and differentiation potential, phenotypic profile and long-term capacity to sustain in vitro hemopoiesis were considered in relation to the different expansion protocols. Results The results showed that angiogenic supplements used in combination with low serum content gave rise to the appearance of Thy-1- HM-MSC with high proliferative potential, capable of restoring the typical HM stromal impairment. The expression of the CD271 was partially maintained. We further report an enhancement towards the osteogenic and adipogenic differentiation capacity by the Thy-1- HM-MSC subset. Despite the angiogenic treatment, the Thy-1- MSC stopped short of full endothelial differentiation. Discussion In this paper we provide evidence that in vitro angiogenic stimuli generate HM-MSC lacking CD90 Ag expression. The Thy-1- MSC subset is characterized by peculiar functional and phenotypic characteristics, thus supporting the role played by the microenvironment in selecting particular hMSC subsets maintaining normal tissue homeostasis or inducing pathologic processes.