In vivo Neuroregeneration to Treat Ischemic Stroke Through NeuroD1 AAV-Based Gene Therapy in Adult Non-human Primates

	In vivo Neuroregeneration to Treat Ischemic Stroke Through NeuroD1 AAV-Based Gene Therapy in Adult Non-human Primates
	Ge, Long-Jiao; Yang, Fu-Han; Li, Wen; Wang, Tao; Lin, Yu; Feng, Jie; Chen, Nan-Hui; Jiang, Min; Wang, Jian-Hong; Hu, Xin-Tian; Chen, Gong
	2020
发表期刊	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
ISSN	2296-634X
卷号	8
摘要	Stroke may cause severe death and disability but many clinical trials have failed in the past, partially because the lack of an effective method to regenerate new neurons after stroke. In this study, we report an in vivo neural regeneration approach through AAV NeuroD1-based gene therapy to repair damaged brains after ischemic stroke in adult non-human primates (NHPs). We demonstrate that ectopic expression of a neural transcription factor NeuroD1 in the reactive astrocytes after monkey cortical stroke can convert 90% of the infected astrocytes into neurons. Interestingly, astrocytes are not depleted in the NeuroD1-converted areas, consistent with the proliferative capability of astrocytes. Following ischemic stroke in monkey cortex, the NeuroD1-mediated astrocyte-to-neuron (AtN) conversion significantly increased local neuronal density, reduced microglia and macrophage, and surprisingly protected parvalbumin interneurons in the converted areas. Furthermore, the NeuroD1 gene therapy showed a broad time window in AtN conversion, from 10 to 30 days following ischemic stroke. The cortical astrocyte-converted neurons showed Tbr1(+) cortical neuron identity, similar to our earlier findings in rodent animal models. Unexpectedly, NeuroD1 expression in converted neurons showed a significant decrease after 6 months of viral infection, indicating a downregulation of NeuroD1 after neuronal maturation in adult NHPs. These results suggest that in vivo cell conversion through NeuroD1-based gene therapy may be an effective approach to regenerate new neurons for tissue repair in adult primate brains.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12889
专题	科研部门_神经系统编码（胡新天）
推荐引用方式 GB/T 7714	Ge, Long-Jiao,Yang, Fu-Han,Li, Wen,et al. In vivo Neuroregeneration to Treat Ischemic Stroke Through NeuroD1 AAV-Based Gene Therapy in Adult Non-human Primates[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2020,8.
APA	Ge, Long-Jiao.,Yang, Fu-Han.,Li, Wen.,Wang, Tao.,Lin, Yu.,...&Chen, Gong.(2020).In vivo Neuroregeneration to Treat Ischemic Stroke Through NeuroD1 AAV-Based Gene Therapy in Adult Non-human Primates.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,8.
MLA	Ge, Long-Jiao,et al."In vivo Neuroregeneration to Treat Ischemic Stroke Through NeuroD1 AAV-Based Gene Therapy in Adult Non-human Primates".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 8(2020).

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2021102503.pdf（16627KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文