Neural Stem Cell-Derived Exosomal Netrin1 Contributes to Neuron Differentiation of Mesenchymal Stem Cells in Therapy of Spinal Bifida Aperta.
Neural Stem Cell-Derived Exosomal Netrin1 Contributes to Neuron Differentiation of Mesenchymal Stem Cells in Therapy of Spinal Bifida Aperta.
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神经干细胞衍生的外泌体 Netrin1 在脊柱裂治疗中有助于间充质干细胞的神经元分化
DOI：
10.1093/stcltm/szac009
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发表时间：
2022-05-27
影响因子：
6
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中科院分区：
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开放性脊柱裂是一种发病率较高的先天性畸形。骨髓间充质干细胞（BMSC）移植具有修复受损组织结构和恢复其功能的潜力。这是一种可选的治疗方法，可作为SBA治疗中手术的补充。然而，BMSCs的应用受到限制，因为BMSCs的神经元分化率在用于治疗严重SBA时并不令人满意。因此，我们的目的是评估神经干细胞（NSC）来源的外泌体对BMSC神经元分化的影响，并观察在离体大鼠SBA胚胎模型中的治疗效果。我们发现，神经干细胞来源的外泌体增加了体外和体外SBA胚胎模型中BMSCs的神经元分化率。蛋白质组学分析表明，神经干细胞衍生的外泌体富含Netrin 1，其正调控神经元分化。Netrin 1可促进BMSCs和NSCs向神经元分化，并上调神经元标记物微管相关蛋白（Map 2）、神经丝蛋白和β3-微管蛋白的表达。生物信息学分析表明，Netrin 1处理增加了与神经元分化相关的转录因子Hand 2和Phox 2b的表达。此外，Netrin 1诱导的NSC神经元分化被Phox 2b敲低显著阻断。我们认为，神经干细胞来源的外泌体Netrin 1诱导神经元分化通过Hand 2/Phox 2b轴上调表达的Hand 2和Phox 2b。因此，NSC衍生的外泌体是BMSC神经元分化的关键诱导剂，并且代表可以有益于SBA中BMSC治疗的潜在治疗剂。
Spinal bifida aperta (SBA) is a congenital malformation with a high incidence. Bone marrow mesenchymal stem cell (BMSC) transplantation has the potential to repair the structure of damaged tissues and restore their functions. This is an optional treatment that can be used as a supplement to surgery in the treatment of SBA. However, the application of BMSCs is limited, as the neuronal differentiation rate of BMSCs is not satisfactory when used in treating severe SBA. Thus, we aimed to assess the effect of neural stem cell (NSC)-derived exosomes on BMSC neuronal differentiation and observe the therapeutic effect in an ex vivo rat SBA embryo model. We found that NSC-derived exosomes increased the neuronal differentiation rate of BMSCs in vitro and in the SBA embryo model ex vivo. Proteomic analysis showed that NSC-derived exosomes were enriched in Netrin1, which positively regulated neuronal differentiation. Netrin1 increased the neuronal differentiation rate of BMSCs and NSCs and upregulated the expression of the neuronal markers, microtubule-associated protein (Map2), neurofilament, and β3-tubulin. Bioinformatic analysis revealed that Netrin1 treatment increased the expression of the transcription factors Hand2 and Phox2b, related to neuronal differentiation. Furthermore, the Netrin1-induced NSC neuronal differentiation was significantly blocked by Phox2b knockdown. We suggest that NSC-derived exosomal Netrin1 induces neuronal differentiation via the Hand2/Phox2b axis by upregulating the expression of Hand2 and Phox2b. Therefore, NSC-derived exosomes are a critical inducer of BMSC neuronal differentiation and represent a potential treatment agent that can benefit BMSC treatment in SBA.
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DOI：
10.1007/978-1-61779-815-3_10
发表时间：
2012-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Lescaudron, Laurent;Boyer, C;Dunbar, G L
通讯作者：
Dunbar, G L
影响因子：
5.3
作者：
Boyer NP;Gupton SL
通讯作者：
Gupton SL
DOI：
10.1007/978-0-387-76715-4_2
发表时间：
2007-01-01
期刊：
AXON GROWTH AND GUIDANCE
影响因子：
--
作者：
Moore, Simon W.;Tessier-Lavigne, Marc;Kennedy, Timothy E.
通讯作者：
Kennedy, Timothy E.
影响因子：
2.4
作者：
Feng, Christina;Graham, Christopher D.;Fauza, Dario O.
通讯作者：
Fauza, Dario O.
影响因子：
25
作者：
通讯作者：
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