Abstract
Korean mistletoe (Viscum album L. var. coloratum) lectin (VCA) is known as an anticancer drug. However, it is not clear whether VCA affects the self-renewal activity of mesenchymal stem cells (MSCs). Therefore, the objectives of this study were to analyze the effect of VCA on the proliferation of MSCs and expression of stemness markers. We also evaluated the usefulness of placenta-derived MSCs (PD-MSCs) as a screening tool. VCA was stably administered to MSCs, and analyzed self-renewal activities. The effect of IL-6 signaling on MSC proliferation was explored by quantitative methylation-specific PCR (qMSP) and western blot analysis. Compared with the control condition, low concentrations of VCA (10 pg/mL) induced an increase in the self-renewal activity of MSCs. Interestingly, a low concentration of VCA promoted IL-6 signaling in PD-MSCs through altered IL-6/STAT3 gene methylation. Furthermore, inhibition of IL-6 expression in PD-MSCs using an anti-IL-6 antibody caused a decrease in their self-renewal activity through IL-6/STAT3 signaling by altering IL-6/STAT3 gene methylation. These findings provide helpful data for understanding the mechanism of MSC self-renewal via VCA and show that VCA may be useful as a functional natural product for developing efficient therapies using placenta-derived stem cells.
Highlights
The mesenchymal stem cells (MSCs) isolated from various adult tissues are used in cell therapy for degenerative disease because these cells have the potential to differentiate into cells of the mesenchymal lineage [1] and exert a therapeutic effect [2]
Differentiation of the placenta-derived mesenchymal stem cells (PD-MSCs) into hepatocytes was evaluated by indocyanine green (ICG) uptake and Periodic acid-Schiff (PAS) staining
We showed that the demethylation of IL-6 and STAT3 induced by low concentrations of VCA increased the proliferation of MSCs via IL-6/STAT3 signaling
Summary
The mesenchymal stem cells (MSCs) isolated from various adult tissues are used in cell therapy for degenerative disease because these cells have the potential to differentiate into cells of the mesenchymal lineage (e.g., chondrocytes, adipocytes and osteoblasts) [1] and exert a therapeutic effect [2]. The limited self-renewal activity of MSCs, which contrasts with the unlimited self-renewal of embryonic stem cells (ESCs), is one hurdle for cell therapies that use MSCs. Recently, placenta-derived mesenchymal stem cells (PD-MSCs) were highlighted as alternative cell sources of bone marrow-derived MSCs (BM-MSCs) because their self-renewal activity is more powerful than that of BM-MSCs [6]. PD-MSCs are consistently maintained from the placenta after full-term birth at the same starting point [6,7,8], though there are still obstacles to enhancing the limited self-renewal of PD-MSCs
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