Mechanisms of the Immunomodulation Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Facial Nerve Injury in Sprague–Dawley Rats

Abstract Background N-hexane, with its metabolite 2,5-hexanedine (HD), is an industrial hazardous material. Chronic hexane exposure causes segmental demyelination in the peripheral nerves, and high-dose intoxication may also affect central nervous system. Demyelinating conditions are difficult to treat and stem cell therapy using bone marrow mesenchymal stem cells (BMSCs) is a promising novel strategy. Our previous study found that BMSCs promoted motor function recovery in rats modeling hexane neurotoxicity. This work aimed to explore the underlying mechanisms and focused on the changes in spinal cord. Methods Sprague Dawley rats were intoxicated with HD (400 mg/kg/day, i.p, for 5 weeks). A bolus of BMSCs (5 × 107 cells/kg) was injected via tail vein. Demyelination and remyelination of the spinal cord before and after BMSC treatment were examined microscopically. Cultured oligodendrocyte progenitor cells (OPCs) were incubated with HD ± BMSC-derived conditional medium (BMSC-CM). OPC differentiation was studied by immunostaining and morphometric analysis. The expressional changes of Hes1, a transcription factor negatively regulating OPC-differentiation, were studied. The upstream Notch1 and TNFα/RelB pathways were studied, and some key signaling molecules were measured. The correlation between neurotrophin NGF and TNFα was also investigated. Statistical significance was evaluated using one-way ANOVA and performed using SPSS 13.0. Results The demyelinating damage by HD and remyelination by BMSCs were evidenced by electron microscopy, LFB staining and NG2/MBP immunohistochemistry. In vitro cultured OPCs showed more differentiation after incubation with BMSC-CM. Hes1 expression was found to be significantly increased by HD and decreased by BMSC or BMSC-CM. The change of Hes1 was found, however, independent of Notch1 activation, but dependent on TNFα/RelB signaling. HD was found to increase TNFα, RelB and Hes1 expression, and BMSCs were found to have the opposite effect. Addition of recombinant TNFα to OPCs or RelB overexpression similarly caused upregulation of Hes1 expression. The secretion of NGF by BMSC and activation of NGF receptor was found important for suppression of TNFα production in OPCs. Conclusions Our findings demonstrated that BMSCs promote remyelination in the spinal cord of HD-exposed rats via TNFα/RelB-Hes1 pathway, providing novel insights for evaluating and further exploring the therapeutical effect of BMSCs on demyelinating neurodegenerative disease.

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Comparative study of allogenic and xenogeneic mesenchymal stem cells on cisplatin-induced acute kidney injury in Sprague-Dawley rats

Stem Cell Research & Therapy ◽

10.1186/s13287-016-0386-0 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 21

Author(s):

Rehab H. Ashour ◽

Mohamed-Ahdy Saad ◽

Mohamed-Ahmed Sobh ◽

Fatma Al-Husseiny ◽

Mohamed Abouelkheir ◽

...

Keyword(s):

Stem Cells ◽

Acute Kidney Injury ◽

Mesenchymal Stem Cells ◽

Comparative Study ◽

Kidney Injury ◽

Sprague Dawley ◽

Sprague Dawley Rats

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Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats

International Journal of Stem Cells ◽

10.15283/ijsc.2016.9.1.70 ◽

2016 ◽

Vol 9 (1) ◽

pp. 70-78 ◽

Cited By ~ 8

Author(s):

Fatma Al-Husseiny ◽

Mohamed Ahmed Sobh ◽

Rehab H. Ashour ◽

Samah Foud ◽

Tarek Medhat ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Amniotic Fluid ◽

Sprague Dawley ◽

Sprague Dawley Rats

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Abstract 2838: Bone Marrow Mesenchymal Stem Cells Differentiated into Beating Cardiomyocytes In Vivo and Improved Myocardial Function

Circulation ◽

10.1161/circ.116.suppl_16.ii_631-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Tong Wang ◽

Wanchun Tang ◽

Shijie Sun ◽

Min-shan Tsai ◽

Max Harry Weil

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Myocardial Function ◽

Phosphate Buffer Solution ◽

Sprague Dawley ◽

Buffer Solution ◽

Marrow Mesenchymal Stem Cells ◽

And Control

Background: In settings of heart failure, infusion of bone marrow mesenchymal stem cells (MSCs) improves myocardial function both in experimental and clinical studies. The mechanism by which MSCs improve myocardial function remains unknown. Hypothesis: MSCs may differentiate into beating myocytes in vivo. The contractility of these cells is comparable with those of myocytes. Methods: A thoracotomy was performed in 10 male Sprague-Dawley rats, weighing 350 – 450g. Myocardial infarction was induced by ligation of the left anterior descending artery (LAD). One week later, animals were randomized to receive 5×10 6 MSCs marked with PKH26 in phosphate buffer solution (PBS) or as a PBS bolus injection into local infarcted myocardium. Six weeks after the MSCs or PBS injection, the hearts were harvested and digested with collagease type II and single cardiomyocytes were obtained. PKH26 labeled myocytes differentiating from MSCs were observed with a microscope Olympus I×71. The contractility of labeled and unlabeled beating cells in MSCs-treated animals was compared. The contractility of unlabeled myocytes was compared between MSCs-treated and control groups. Result: The beating fluorescent labeled myocytes can be found in MSCs-treated animals [(1.2±0.4) ×10 6 ] and contractility of these cells were the same as that of unlabeled beating myocytes (Table 1 ). The contractility of unlabeled myocytes, however, was significantly better in MSCs-treated animals. Conclusion: MSCs could differentiate into the beating myocytes. However, this may not be the sole mechanism of improved myocardial function. Table 1 Cells contractility (%)

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