Secreted galectin-3 as a possible biomarker for the immunomodulatory potential of human umbilical cord mesenchymal stromal cells

• Published in: Cytotherapy (Oxford, England) Vol. 15; no. 10; pp. 1208 - 1217
• Main Authors: Liu, Guang-Yang, Xu, Yi, Li, Yan, Wang, Li-Hua, Liu, Yong-Jun, Zhu, Delin
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.10.2013
• Subjects: Advanced Basic Science; biomarker; Biomarkers - metabolism; Cell Proliferation; Cells, Cultured; Coculture Techniques; Galectin 3 - genetics; Galectin 3 - metabolism; galectin-3; Gene Expression Regulation - genetics; Humans; Immunomodulation - drug effects; Immunomodulation - genetics; immunomodulatory; Leukocytes, Mononuclear - immunology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - immunology; Other; Recombinant Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering - genetics; Umbilical Cord - cytology; umbilical cord-derived mesenchymal stromal cells; umbilical cord-derived mesenchymal stromal cells; biomarker; galectin-3; immunomodulatory
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2013.05.011

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.