Changes in PTTG1 by human TERT gene expression modulate the self-renewal of placenta-derived mesenchymal stem cells

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.

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H/ACA Box Small Nucleolar RNA 7A Promotes the Self-Renewal of Human Umbilical Cord Mesenchymal Stem Cells

Stem Cells ◽

10.1002/stem.2490 ◽

2016 ◽

Vol 35 (1) ◽

pp. 222-235 ◽

Cited By ~ 10

Author(s):

Yan Zhang ◽

Chen Xu ◽

Daolan Gu ◽

Minjuan Wu ◽

Binghao Yan ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

The Self ◽

Human Umbilical Cord ◽

Small Nucleolar Rna ◽

Self Renewal ◽

Nucleolar Rna

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Heparan Sulfate Enhances the Self-Renewal and Therapeutic Potential of Mesenchymal Stem Cells from Human Adult Bone Marrow

Stem Cells and Development ◽

10.1089/scd.2011.0367 ◽

2012 ◽

Vol 21 (11) ◽

pp. 1897-1910 ◽

Cited By ~ 33

Author(s):

Torben Helledie ◽

Christian Dombrowski ◽

Bina Rai ◽

Zophia X.H. Lim ◽

Ian Lee Hock Hin ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Heparan Sulfate ◽

Therapeutic Potential ◽

The Self ◽

Self Renewal ◽

Adult Bone Marrow ◽

Human Adult ◽

Adult Bone

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Suppression of Androgen Receptor Enhances the Self-renewal of Mesenchymal Stem Cells Through Elevated Expression of EGFR

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ◽

10.1016/j.bbamcr.2013.01.007 ◽

2013 ◽

Vol 1833 (5) ◽

pp. 1222-1234 ◽

Cited By ~ 15

Author(s):

Chiung-Kuei Huang ◽

Meng-Yin Tsai ◽

Jie Luo ◽

Hong-Yo Kang ◽

Soo Ok Lee ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Androgen Receptor ◽

The Self ◽

Self Renewal ◽

Elevated Expression

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Zinc sulfate contributes to promote telomere length extension via increasing telomerase gene expression, telomerase activity and change in the TERT gene promoter CpG island methylation status of human adipose-derived mesenchymal stem cells

PLoS ONE ◽

10.1371/journal.pone.0188052 ◽

2017 ◽

Vol 12 (11) ◽

pp. e0188052 ◽

Cited By ~ 21

Author(s):

Raheleh Farahzadi ◽

Ezzatollah Fathi ◽

Seyed Alireza Mesbah-Namin ◽

Nosratollah Zarghami

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Zinc Sulfate ◽

Cpg Island ◽

Methylation Status ◽

Gene Promoter ◽

Telomerase Activity ◽

Tert Gene ◽

Cpg Island Methylation

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The Flavonoid Glabridin Induces OCT4 to Enhance Osteogenetic Potential in Mesenchymal Stem Cells

Stem Cells International ◽

10.1155/2017/6921703 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

June Seok Heo ◽

Seung Gwan Lee ◽

Hyun Ok Kim

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

The Self ◽

Significant Elevation ◽

Differentiation Potential ◽

Self Renewal ◽

Reverse Transcription Pcr ◽

Promising Tool

Mesenchymal stem cells (MSCs) are a promising tool for studying intractable diseases. Unfortunately, MSCs can easily undergo cellular senescence during in vitro expansion by losing stemness. The aim of this study was to improve the stemness and differentiation of MSCs by using glabridin, a natural flavonoid. Assessments of cell viability, cell proliferation, β-galactosidase activity, differentiation, and gene expression by reverse transcription PCR were subsequently performed in the absence or presence of glabridin. Glabridin enhanced the self-renewal capacity of MSCs, as indicated by the upregulation of the OCT4 gene. In addition, it resulted in an increase in the osteogenic differentiation potential by inducing the expression of osteogenesis-related genes such as DLX5 and RUNX2. We confirmed that glabridin improved the osteogenesis of MSCs with a significant elevation in the expression of OSTEOCALCIN and OSTEOPONTIN genes. Taken together, these results suggest that glabridin enhances osteogenic differentiation of MSCs with induction of the OCT4 gene; thus, glabridin could be useful for stem cell-based therapies.

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A Member of the Nuclear Receptor Superfamily, Designated as NR2F2, Supports the Self-Renewal Capacity and Pluripotency of Human Bone Marrow-Derived Mesenchymal Stem Cells

Stem Cells International ◽

10.1155/2016/5687589 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Ni Zhu ◽

Huafang Wang ◽

Binsheng Wang ◽

Jieping Wei ◽

Wei Shan ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Nuclear Receptor ◽

Adipogenic Differentiation ◽

The Self ◽

Human Bone ◽

Self Renewal ◽

Nuclear Receptor Superfamily ◽

Colony Forming Capacity

Mesenchymal stem cells are characterized with self-renewal capacity and pluripotency. NR2F2 is a nuclear receptor that has been detected in the mesenchymal compartment of developing organs. However, whether NR2F2 plays a role in the stemness maintenance of mesenchymal stem cells has not been explored yet. In this study, we investigated the function of NR2F2 in bone marrow-derived mesenchymal stem cells via shRNA-mediated knock-down of NR2F2. The suppression of NR2F2 impaired the colony-forming efficacy of mesenchymal stem cells. The inhibition of colony-forming capacity may be attributed to the acceleration of senescence through upregulation of P21 and P16. The downregulation of NR2F2 also suppressed both osteogenic and adipogenic differentiation processes. In conclusion, NR2F2 plays an important role in the stemness maintenance of bone marrow-derived mesenchymal stem cells.

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