Sensory neuron differentiation potential of in utero mesenchymal stem cell transplantation in rat fetuses with spina bifida aperta
Sensory neuron differentiation potential of in utero mesenchymal stem cell transplantation in rat fetuses with spina bifida aperta
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宫内间充质干细胞移植对先天性脊柱裂大鼠胎儿感觉神经元分化潜能的影响
DOI：
10.1002/bdra.23401
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发表时间：
2015-09-01
影响因子：
--
通讯作者：
Yuan, Zhengwei
中科院分区：
文献类型：
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作者：
Ma, Wei;Wei, Xiaowei;Yuan, Zhengwei
背景在以前的研究中，我们发现感觉和运动神经元的缺乏是与脊柱畸形相关的主要缺陷。在维甲酸诱导的脊柱裂大鼠模型中，通过子宫内干细胞移植对脊柱裂进行产前治疗后，我们发现间充质干细胞（MSCs）存活、迁移并分化为神经系细胞。在本研究中，我们调查了移植的MSC是否有潜力分化成感觉神经元或保护感觉神经元在有缺陷的spinal cord. METHODS妊娠大鼠用维甲酸处理胚胎天（E）10，进行胚胎手术MSC移植E16。在E20收获胎仔。免疫荧光法检测移植的MSCs和脊髓背根节（DRG）神经元中Brn 3a蛋白的表达。采用实时聚合酶链反应分析转录因子Brn 3a和Runx 1在脊髓中的表达。结果部分移植的MSC表达感觉神经元细胞特异性表型。与对照组相比，Brn 3a和Runx 1的表达在有缺陷的脊髓中上调。移植后DRG内Brn 3a阳性神经元的比例也明显增加。结论骨髓间充质干细胞脊髓内移植可促进移植的骨髓间充质干细胞及其周围细胞向感觉神经元细胞方向分化，对保护DRG内感觉神经元起重要作用。这种方法可能对治疗开放性脊柱裂感觉神经元缺陷有价值。出生缺陷研究（A部分）103：772-779，2015年。(c)2015 Wiley Periodicals，Inc.
BACKGROUNDIn previous studies, we found that the deficiency of sensory and motor neurons was a primary defect associated with the spinal malformation. Upon prenatal treatment of spina bifida through in utero stem cell transplantation in a retinoic acid-induced spina bifida rat model, we found that the mesenchymal stem cell (MSCs) survived, migrated, and differentiated into cells of a neural lineage. In the present study, we investigated whether the transplanted MSCs had the potential to differentiate into sensory neurons or to protect sensory neurons in the defective spinal cord.METHODSPregnant rats treated with retinoic acid on embryonic day (E) 10, underwent fetal surgery for MSC transplantation on E16. The fetuses were harvested on E20. Immunofluorescence was used to detect the expression of Brn3a protein in the transplanted MSCs and dorsal root ganglion (DRG) neurons in the defective spinal cords. The expression of the transcription factors Brn3a and Runx1 in spinal cords was analyzed using real-time polymerase chain reaction.RESULTSSome of the transplanted MSCs expressed sensory neuron cell specific phenotypes. The expression of Brn3a and Runx1 was upregulated in the defective spinal cords when compared to controls. The percentage of Brn3a-positive neurons in DRG was also increased after transplantation.CONCLUSIONOur results indicate that the transplantation of MSCs into the spinal cord could promote the transplanted MSCs and the surrounding cells to differentiate toward a sensory neuron cell fate and to play an important role in protecting sensory neurons in DRG. This approach might be of value in the treatment of sensory neuron deficiency in spina bifida aperta. Birth Defects Research (Part A) 103:772-779, 2015. (c) 2015 Wiley Periodicals, Inc.