Conversion of monkey fibroblasts to transplantable telencephalic neuroepithelial stem cells
Conversion of monkey fibroblasts to transplantable telencephalic neuroepithelial stem cells
复制标题
猴成纤维细胞向可移植端脑神经上皮干细胞的转化
DOI：
10.1016/j.biomaterials.2015.10.079
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发表时间：
2016-01-01
期刊：
影响因子：
14
通讯作者：
Li, Tianqing
中科院分区：
文献类型：
--
作者：
Ai, Zongyong;Xiang, Zheng;Li, Tianqing
非人类灵长类动物为干细胞疗法的发展提供了最佳模型。虽然体细胞已被转化为神经干细胞/祖细胞，但在灵长类动物中，成纤维细胞能否产生具有稳定性质的端脑神经上皮干细胞（NESCs）尚不清楚。本文报道了转录因子（Oct4, Sox2, Klf4）与一种新型培养基的结合诱导恒河猴成纤维细胞形成NESCs，并在细胞水平上发育成微型神经管（NT）样结构。此外，单次诱导的NESCs （iNESCs）在基质上悬浮培养后可以产生后期3D-NTs。iNESCs表达NT细胞标记物，具有偏向端脑区模式的独特基因表达模式，并产生皮层神经元。通过移植，单个iNESCs可以在成年猴纹状体和皮层中广泛存活，再生髓鞘神经元轴突和突触结构，并分化为皮质神经元。移植的成功与否与移植区和移植细胞的特性密切相关。在确定的条件下，从灵长类成纤维细胞中产生确定的和可移植的iNESCs，具有可预测的命运选择的能力，将促进疾病建模和细胞治疗。(C) 2015 Elsevier Ltd.版权所有。
Non-human primates provide optimal models for the development of stem cell therapies. Although somatic cells have been converted into neural stem/progenitor cells, it is unclear whether telencephalic neuroepithelial stem cells (NESCs) with stable properties can be generated from fibroblasts in primate. Here we report that a combination of transcription factors (Oct4, Sox2, Klf4) with a new culture medium induces rhesus monkey fibroblasts into NESCs, which can develop into miniature neural tube (NT)-like structures at a cell level. Furthermore, single induced NESCs (iNESCs) can generate later-stage 3D-NTs after grown on matrigel in suspension culture. iNESCs express NT cell markers, have a unique gene expression pattern biasing towards telencephalic patterning, and give rise to cortical neurons. Via transplantation, single iNESCs can extensively survive, regenerate myelinated neuron axons and synapse structures in adult monkey striatum and cortex, and differentiate into cortical neurons. Successful transplantation is closely associated with graft regions and grafted cell identities. The ability to generate defined and transplantable iNESCs from primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and cell therapy. (C) 2015 Elsevier Ltd. All rights reserved.