scholarly journals Effect of Hypoxia on the Differentiation and the Self-Renewal of Metanephrogenic Mesenchymal Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Shaopeng Liu ◽  
Nana Song ◽  
Jianqiang He ◽  
Xiaofang Yu ◽  
Jia Guo ◽  
...  

Hypoxia is an important and influential factor in development. The embryonic kidney is exposed to a hypoxic environment throughout its development. The Wnt/β-catenin pathway plays vital roles in the differentiation and self-renewal of metanephrogenic mesenchymal stem cells (MMSCs) from which the kidney is derived. Thus, we hypothesized that hypoxia can regulate the differentiation and pluripotency of MMSCs through the Wnt/β-catenin pathway. To test this hypothesis, MMSCs from rats at embryonic day 18.5 were cultured in normoxic (21% O2) and hypoxic (1% O2) conditions. The effects of hypoxia on differentiation, stemness, proliferation, and apoptosis of cultured MMSCs and on the activity of the Wnt/β-catenin pathway were tested. Our results revealed that the hypoxic condition increased the number of epithelial cells (E-cadherin+ or CK18+) as well the expression of markers of renal tubule epithelia cells (CDH6, Aqp1, and OPN), decreased the number and proliferation of stem cells (SIX-2+ or CITED1+), and induced apoptosis. Additionally, hypoxia reduced the expression of Wnt4 as well as its downstream molecules β-catenin, LEF-1, and Axin2. Activation of the Wnt/β-catenin pathway by LiCl or BIO modified the effects of hypoxia on the differentiation and self-renewal of MMSCs. Thus, we concluded that hypoxia induces the differentiation and inhibits the self-renewal of MMSCs by inhibiting the Wnt/β-catenin pathway. The observations further our understanding of the effects of hypoxia on kidney.

2016 ◽  
Vol 5 (6) ◽  
pp. 702-710 ◽  
Author(s):  
Jichuan Qiu ◽  
Deshuai Li ◽  
Xiaoning Mou ◽  
Jianhua Li ◽  
Weibo Guo ◽  
...  

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2604 ◽  
Author(s):  
Kim ◽  
Choi ◽  
Lim ◽  
Jun ◽  
Moon ◽  
...  

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.


2014 ◽  
Vol 357 (1) ◽  
pp. 145-157 ◽  
Author(s):  
Hyun-Jung Lee ◽  
Jong-Ho Choi ◽  
Jieun Jung ◽  
Jin Kyeoung Kim ◽  
Sang Shin Lee ◽  
...  

Stem Cells ◽  
2016 ◽  
Vol 35 (1) ◽  
pp. 222-235 ◽  
Author(s):  
Yan Zhang ◽  
Chen Xu ◽  
Daolan Gu ◽  
Minjuan Wu ◽  
Binghao Yan ◽  
...  

2012 ◽  
Vol 21 (11) ◽  
pp. 1897-1910 ◽  
Author(s):  
Torben Helledie ◽  
Christian Dombrowski ◽  
Bina Rai ◽  
Zophia X.H. Lim ◽  
Ian Lee Hock Hin ◽  
...  

2013 ◽  
Vol 1833 (5) ◽  
pp. 1222-1234 ◽  
Author(s):  
Chiung-Kuei Huang ◽  
Meng-Yin Tsai ◽  
Jie Luo ◽  
Hong-Yo Kang ◽  
Soo Ok Lee ◽  
...  

2021 ◽  
Author(s):  
Yang Xiaofeng ◽  
Qianqian Wang

Abstract Objective: To investigate the survival ability of bone marrow Mesenchymal stem cells (MSCs) transfected with survinvin gene in the microenvironment of renal ischemia,and to study the ability and mechanism of repairing renal ischemia-reperfusion injury in rats.Method: Mesenchymal stem cells (MSCs) from bone marrow of male Sprague–Dawley rat were infected with the self‐inactive lentiviral vector and transfected with the Survinvin gene recombinant vector and then EGFP-tagged. After amplification and culture, they were detected by green fluorescence and then retained.48 specific pathogen-free C57BL/6J mice were randomly divided into 4 groups of 12 each. Rats in the control group were only surgically exposed. The other 3 groups were surgically exposed and the bilateral renal arteries were clamped for 45 minutes to restore blood supply, and models of renal ischemia-reperfusion were established. There were control group,ischemia reperfusion group(Marked as IR group), empty virus transfection transplantation group(Marked as MSCs group) or survinvin gene transfection transplantation group(Marked as SVV/MSCs group), and sequentially injected with normal saline,normal saline,1×106 MSCs infected with the self‐inactive lentiviral vector or 1×106 survivin gene-expressing MSCs. At different time points of 1d, 3d, 7d, 14d, collect serum to test blood urea nitrogen detection, to cut the rat kidney section for quantitative analysis, HE staining to observe renal issues changes and the degree of renal tubular damage and IL-10 by using ELISA detection. Result: The MSCs with resuscitation and expansion culture had strong proliferation and good fluorescence. The creatinine urea nitrogen level in the MSCs group and SVV/MSCs group was significantly lower than that in the IR group and control group (p<0.01 or p<0.05). The pathological damage score of HE staining in the kidney was lighter in the stem cell transplantation group, and the SVV/MSCs group was significantly lower than the other two groups (p<0.01 or p<0.05). On the 3rd and 14th day, the number of transplanted cells in the kidney tissue was much higher in the SVV/MSCs group than in the MSCs group. The MSCs expressing EGFP were mainly distributed around the glomerulus, the small vessel inner wall, and the interstitial between the renal tubule and the renal tubule. However, MSCs expressing EGFP were hardly seen on the inner wall of the renal tubule. The levels of protective factors IL-10 increased after renal ischemic injury. SVV/MSCs group was also significantly more than IR group or MSCs group (P<0.01 or p<0.05). And there was no statistical difference from the normal control group on the 14th day.Conclusion: Transfection of Survinifin gene can increase the survival ability of MSCs in ischemic kidney. After transplantation, MSCs are not directly differentiated into injured tubular endothelial cells, which further promote the repair of kidney damage through its strong paracrine effect.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
June Seok Heo ◽  
Seung Gwan Lee ◽  
Hyun Ok Kim

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Ni Zhu ◽  
Huafang Wang ◽  
Binsheng Wang ◽  
Jieping Wei ◽  
Wei Shan ◽  
...  

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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