Guang-Yang Liu1, Yi Xu, Yan Li, Li-Hua Wang, Yong-Jun Liu, Delin Zhu. 1. Key Laboratory of Systems Bioengineering, Ministry of Education and Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
Abstract
BACKGROUND AIMS: Human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) possess broad and potent immunomodulatory activities and have shown great potential in anti-inflammatory therapies. However, a biomarker that can be used to assess quickly and efficiently the immunomodulatory function of UC-MSCs has not been identified. Several studies have revealed that galectin-3 (Gal-3), a member of the human galectin family, is involved in the immunosuppressive function of MSCs. METHODS: Gal-3 gene expression in UC-MSCs was analyzed using quantitative reverse transcriptase polymerase chain reaction and Western blotting. Blocking of Gal-3 expression in UC-MSCs with small interfering RNA was employed to analyze whether the immunosuppressive function of UC-MSCs was affected. RESULTS: We found that UC-MSCs expressed Gal-3 both on the cell surface and in secreted form, and the expression levels of Gal-3 did not show significant variation after cell passaging. We further showed that Gal-3 expression correlated with the immunosuppressive function of UC-MSCs because knock-down of Gal-3 expression with small interfering RNA significantly abrogated the inhibitory effects of UC-MSCs on mitogen-stimulated and alloantigen-stimulated proliferation of human peripheral blood mononuclear cells; meanwhile, the inhibitory effect of UC-MSCs was reversed by adding back recombinant Gal-3 to the co-culture systems. The inhibitory activities of human UC-MSCs were not reduced even when they were separated from human peripheral blood mononuclear cells in a transwell co-culture system, indicating that the soluble form of Gal-3 was the major effector. CONCLUSIONS: The Gal-3 protein secreted by UC-MSCs shows good correlation with immunosuppressive potential and may serve as a possible biomarker for the potency test of UC-MSCs.
BACKGROUND AIMS: Human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) possess broad and potent immunomodulatory activities and have shown great potential in anti-inflammatory therapies. However, a biomarker that can be used to assess quickly and efficiently the immunomodulatory function of UC-MSCs has not been identified. Several studies have revealed that galectin-3 (Gal-3), a member of the human galectin family, is involved in the immunosuppressive function of MSCs. METHODS:Gal-3 gene expression in UC-MSCs was analyzed using quantitative reverse transcriptase polymerase chain reaction and Western blotting. Blocking of Gal-3 expression in UC-MSCs with small interfering RNA was employed to analyze whether the immunosuppressive function of UC-MSCs was affected. RESULTS: We found that UC-MSCs expressed Gal-3 both on the cell surface and in secreted form, and the expression levels of Gal-3 did not show significant variation after cell passaging. We further showed that Gal-3 expression correlated with the immunosuppressive function of UC-MSCs because knock-down of Gal-3 expression with small interfering RNA significantly abrogated the inhibitory effects of UC-MSCs on mitogen-stimulated and alloantigen-stimulated proliferation of human peripheral blood mononuclear cells; meanwhile, the inhibitory effect of UC-MSCs was reversed by adding back recombinant Gal-3 to the co-culture systems. The inhibitory activities of human UC-MSCs were not reduced even when they were separated from human peripheral blood mononuclear cells in a transwell co-culture system, indicating that the soluble form of Gal-3 was the major effector. CONCLUSIONS: The Gal-3 protein secreted by UC-MSCs shows good correlation with immunosuppressive potential and may serve as a possible biomarker for the potency test of UC-MSCs.
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