The Effect of Myostatin (GDF-8) on Proliferation and Tenocyte Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells

2017 ◽  
Vol 22 (02) ◽  
pp. 200-207 ◽  
Author(s):  
Wei Le ◽  
Jeffrey Yao
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Sprague Dawley ◽  
Repair Site ◽  
Migration Assay ◽  
Immunohistochemistry Staining ◽  
Rat Bone

Background: The future in flexor tendon surgery involves tissue engineering approaches directed toward increasing early repair strength to accelerate tendon healing and to allow for earlier onset of rehabilitation. Previous work has shown that pluripotential mesenchymal stem cells may be successfully delivered to a tendon repair site using a suture carrier. The current work describes the use of Myostatin (GDF-8) to help guide these delivered pluripotential stem cells to differentiate down a tenocyte lineage to potentially maximize the reparative effects of these cells at the tendon repair site.Methods: Primary rat bone marrow mesenchymal stem cells isolated from the long bones of male Sprague-Dawley rats were treated with 500 ng/ml myostatin for 24 h, 48 h, and 72 h. Collagen 1 A, scleraxis (Scx), and tenomodulin (Tnmd) expression, indicative of tenogenesis, was analyzed using real time PCR and immunohistochemistry staining. A migration assay was performed to assess the functional activity of BMSCs after they were treated with myostatin.Results: Compared to the control cells (without treatment), the cells treated with 500 ng/ml myostatin for 72 h exhibited higher expression of Col 1A, Scx, and Tnmd. The mRNA expression of Col1A, Scx, Tnmd increased 15.3, 13 and 7 times respectively. Immunohistochemistry staining showed Scx and Tnmd were expressed in the cellular cytoplasm. In response to myostatin, the cells also showed a tendency to proliferate and migrate more than the control cells.Conclusions: Myostatin (GDF-8) has the ability to increase rat bone marrow mesenchymal stem cell growth and differentiation toward a tenocyte lineage. This information could be useful for future studies regarding tendon repair.

scholarly journals Characterization and Expression of Senescence Marker in Prolonged Passages of Rat Bone Marrow-Derived Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Noridzzaida Ridzuan ◽  
Akram Al Abbar ◽  
Wai Kien Yip ◽  
Maryam Maqbool ◽  
Rajesh Ramasamy
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
In Vitro Culture ◽  
Cellular Senescence ◽  
Sprague Dawley ◽  
Lineage Differentiation ◽  
Rat Bone

The present study is aimed at optimizing the in vitro culture protocol for generation of rat bone marrow- (BM-) derived mesenchymal stem cells (MSCs) and characterizing the culture-mediated cellular senescence. The initial phase of generation and characterization was conducted using the adherent cells from Sprague Dawley (SD) rat’s BM via morphological analysis, growth kinetics, colony forming unit capacity, immunophenotyping, and mesodermal lineage differentiation. Mesenchymal stem cells were successfully generated and characterized as delineated by the expressions of CD90.1, CD44H, CD29, and CD71 and lack of CD11b/c and CD45 markers. Upon induction, rBM-MSCs differentiated into osteocytes and adipocytes and expressed osteocytes and adipocytes genes. However, a decline in cell growth was observed at passage 4 onwards and it was further deciphered through apoptosis, cell cycle, and senescence assays. Despite the enhanced cell viability at later passages (P4-5), the expression of senescence marker,β-galactosidase, was significantly increased at passage 5. Furthermore, the cell cycle analysis has confirmed the in vitro culture-mediated cellular senescence where cells were arrested at the G0/G1phase of cell cycle. Although the currently optimized protocols had successfully yielded rBM-MSCs, the culture-mediated cellular senescence limits the growth of rBM-MSCs and its potential use in rat-based MSC research.

Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis

2018 ◽  
Vol 18 ◽  
Author(s):  
Chaitra Venugopal ◽  
Christopher Shamir ◽  
Sivapriya Senthilkumar ◽  
Janitri Venkatachala Babu ◽  
Peedikayil Kurien Sonu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Neuroprotective Effects ◽  
Marrow Mesenchymal Stem Cells ◽  
Vitro Analysis ◽  
In Vitro Analysis ◽  
Rat Bone

Characterization of mesenchymal stem cells from rat bone marrow: ultrastructural properties, differentiation potential and immunophenotypic markers

2009 ◽  
Vol 132 (5) ◽  
pp. 533-546 ◽  
Author(s):  
Erdal Karaoz ◽  
Ayça Aksoy ◽  
Selda Ayhan ◽  
Ayla Eker Sarıboyacı ◽  
Figen Kaymaz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Differentiation Potential ◽  
Rat Bone

Malignant transformation of rat bone marrow-derived mesenchymal stem cells treated with 4-nitroquinoline 1-oxide

2010 ◽  
Vol 188 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Shujuan Zhang ◽  
Zhijuan Han ◽  
Qingfei Kong ◽  
Jinghua Wang ◽  
Bo Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Malignant Transformation ◽  
Rat Bone

scholarly journals Bone marrow mesenchymal stem cells promote remyelination in spinal cord by driving oligodendrocyte progenitor cell differentiation via TNFα/RelB-Hes1 pathway: a rat model study of 2,5-hexanedione-induced neurotoxicity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shuangyue Li ◽  
Huai Guan ◽  
Yan Zhang ◽  
Sheng Li ◽  
Kaixin Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Statistical Significance ◽  
High Dose ◽  
Sprague Dawley ◽  
Oligodendrocyte Progenitor ◽  
Hes1 Expression ◽  
Marrow Mesenchymal Stem Cells

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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