Transamniotic mesenchymal stem cell therapy for neural tube defects preserves neural function through lesion-specific engraftment and regeneration
Transamniotic mesenchymal stem cell therapy for neural tube defects preserves neural function through lesion-specific engraftment and regeneration
复制标题
经羊膜间充质干细胞治疗神经管缺陷可通过病变特异性植入和再生来保留神经功能
DOI：
10.1038/s41419-020-2734-3
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Zhengwei Yuan
中科院分区：
文献类型：
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作者：
Xiaowei Wei;Wei Ma;Hui Gu;Dan Liu;Wenting Luo;Yuzuo Bai;Weilin Wang;Vincent Chi Hang Lui;Peixin Yang;Zhengwei Yuan
神经管缺陷（NTDs）导致产前死亡率和终身发病率。目前，手术闭合NTD病变导致功能恢复有限。我们以前认为神经再生是NTD治疗的关键。在这里，我们报告，经羊膜骨髓间充质干细胞（BMSC）治疗NTDs在早期发展可能会实现有益的功能恢复。在我们的离体大鼠胚胎NTD模型中，注入羊膜腔的BMSCs自发迁移到有缺陷的神经组织中。肝细胞生长因子及其受体c-MET被发现在这种NTD病变特异性迁移中发挥关键作用。利用体内大鼠胎儿NTD模型，我们进一步发现移植的BMSCs特异性分化为缺陷组织的细胞类型，包括皮肤和原位不同类型的神经元。BMSC治疗引发胎儿皮肤修复，导致皮肤病变面积减少29.9 ± 5.6%。电生理功能恢复试验显示BMSC处理的胎儿潜伏期缩短，运动诱发电位振幅增加。基于这些积极的结果，易于操作，并减少创伤的母亲和胎儿，我们建议，经羊膜BMSC管理可能是一个新的有效的治疗NTDs。
Neural tube defects (NTDs) lead to prenatal mortality and lifelong morbidity. Currently, surgical closure of NTD lesions results in limited functional recovery. We previously suggested that nerve regeneration was critical for NTD therapy. Here, we report that transamniotic bone marrow-derived mesenchymal stem cell (BMSC) therapy for NTDs during early development may achieve beneficial functional recovery. In our ex vivo rat embryonic NTD model, BMSCs injected into the amniotic cavity spontaneously migrated into the defective neural tissue. Hepatocyte growth factor and its receptor c-MET were found to play critical roles in this NTD lesion-specific migration. Using the in vivo rat fetal NTD model, we further discovered that the engrafted BMSCs specifically differentiated into the cell types of the defective tissue, including skin and different types of neurons in situ. BMSC treatment triggered skin repair in fetuses, leading to a 29.9 ± 5.6% reduction in the skin lesion area. The electrophysiological functional recovery assay revealed a decreased latency and increased motor-evoked potential amplitude in the BMSC-treated fetuses. Based on these positive outcomes, ease of operation, and reduced trauma to the mother and fetus, we propose that transamniotic BMSC administration could be a new effective therapy for NTDs.