Programming of human endometrial-derived stromal cells (EnSCs) into pre-oligodendrocyte cells by overexpression of miR-219

Programming of human endometrial-derived stromal cells (EnSCs) into pre-oligodendrocyte cells by overexpression of miR-219
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DOI:
10.1016/j.neulet.2013.01.022
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发表时间:
2013-03-14
影响因子:
2.5
通讯作者:
Massumi, Mohammad
Massumi, Mohammad
中科院分区:
医学4区
文献类型:
--
作者:
Ebrahimi-Barough, Somayeh;Kouchesfehani, Homa Mohseni;Massumi, Mohammad

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少突胶质细胞是中枢神经系统中的髓鞘细胞,形成轴突髓鞘,支持神经快速传导。microrna在少突胶质细胞发育中起着关键作用。多项研究表明,miR-219通过抑制少突胶质细胞发育的负调节因子来促进少突胶质细胞分化是必要的。人子宫内膜源性基质细胞(EnSCs)是一种数量丰富、可用性好的成体干细胞,具有较低的免疫不相容性,可作为细胞替代疗法的研究对象。用FGF2、EGF和PDGF-AA诱导EnSCs后,用表达mir -219- gfp的慢病毒感染EnSCs。分析细胞表达阶段特异性少突胶质细胞标记物。定量RT-PCR和免疫细胞化学分析显示,分期特异性标志物Nestin、Olig2、Sox10、PDGFRa、CNP、A2B5、O4和MBP通过分化协议在其特定阶段表达。结果显示,mir -219- gfp表达细胞中前少突胶质细胞标志物的表达高于三碘甲状腺原氨酸(T3)处理细胞。总之,通过过表达miR-219, EnSCs可以被编程为前少突胶质细胞,并可能使这些细胞被认为是神经退行性疾病细胞替代治疗的安全来源。2013爱思唯尔爱尔兰有限公司版权所有。
Oligodendrocytes are myelinating cells in the central nervous system that form the myelin sheath of axons to support rapid nerve conduction. MicroRNAs have critical roles in oligodendrocyte development. Several studies have shown that miR-219 is necessary to promote oligodendrocyte differentiation through repressing negative regulators of oligodendrocyte development. Human endometrial-derived stromal cells (EnSCs) are abundant and available adult stem cells with low immunological incompatibility, which could be considered for cell replacement therapy in future. After induction of EnSCs by FGF2, EGF and PDGF-AA, they were infected by miR-219-GFP-expressing lentiviruses. The cells were analyzed for expression of stage-specific oligodendrocyte cells markers. Quantitative RT-PCR and immunocytochemistry analyses showed that stage-specific markers Nestin, Olig2, Sox10, PDGFRa, CNP, A2B5, O4, and MBP are expressed in their specific stages through differentiation protocol. Results showed that expression of pre-oligodendrocyte markers in miR-219-GFP-expressing cells were higher than triiodothyronine (T3) treated cells. In conclusion, the EnSCs could be programmed into pre-oligodendrocyte cells by overexpression of miR-219, and may convince to consider these cells as safe source for cell replacement therapy of neurodegenerative diseases. (c) 2013 Elsevier Ireland Ltd. All rights reserved.