Secreted galectin-3 as a Possible Biomarker for the Immunomodulatory Potential of Human Umbilical Cord Mesenchymal Stromal Cells

Cytotherapy. 2013 Oct;15(10):1208-17. doi: 10.1016/j.jcyt.2013.05.011. Epub 2013 Jul 11.

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.

Keywords: biomarker; galectin-3; immunomodulatory; umbilical cord-derived mesenchymal stromal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Gene Expression Regulation / genetics
  • Humans
  • Immunomodulation / drug effects
  • Immunomodulation / genetics
  • Leukocytes, Mononuclear / immunology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology*
  • RNA, Small Interfering / genetics
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Umbilical Cord / cytology

Substances

  • Biomarkers
  • Galectin 3
  • RNA, Small Interfering
  • Recombinant Proteins