Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke

Human cortical neural progenitor cell transplantation holds significant potential in cortical stroke treatment by replacing lost cortical neurons and repairing damaged brain circuits. However, commonly utilized human cortical neural progenitors are limited in yield a substantial proportion of diverse cortical neurons and require an extended period to achieve functional maturation and synaptic integration, thereby potentially diminishing the optimal therapeutic benefits of cell transplantation for cortical stroke. Here, we generated forkhead box G1 (FOXG1)-positive forebrain progenitors from human inducible pluripotent stem cells, which can differentiate into diverse and balanced cortical neurons including upper- and deep-layer excitatory and inhibitory neurons, achieving early functional maturation simultaneously in vitro. Furthermore, these FOXG1 forebrain progenitor cells demonstrate robust cortical neuronal differentiation, rapid functional maturation and efficient synaptic integration after transplantation into the sensory cortex of stroke-injured adult rats. Notably, we have successfully utilized the non-invasive <sup>18</sup>F-SynVesT-1 PET imaging technique to assess alterations in synapse count before and after transplantation therapy of FOXG1 progenitors in vivo. Moreover, the transplanted FOXG1 progenitors improve sensory and motor function recovery following stroke. These findings provide systematic and compelling evidence for the suitability of these FOXG1 progenitors for neuronal replacement in ischemic cortical stroke.

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Publication Details

Journal
Nature Communications
Published
2025-06-03
DOI
https://doi.org/10.1038/s41467-025-60187-5
Citations
10
Primary Topic
Neurogenesis and neuroplasticity mechanisms
Type
article
Field-Weighted Citation Impact
13.19

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article

Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke

A. Cahid Civelek, Peili Cen, Youyou Zhou, Mei Tian et al.
10 citations
Nature Communications
Neurogenesis and neuroplasticity mechanisms
13.19
article

Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke

A. Cahid Civelek, Peili Cen, Youyou Zhou, Mei Tian, Chentao Jin, Fei Huang, Xiaoyun Luo, Xiyi Qin, Jing Fan, Xiaohui Zhang, Mengjiao Tu, Xiao He, Shuang Wu, Rui Zhou, Hong Zhang, Jing Wang, Li Shen, Yu Zhou, Jiadong Chen, Jieqiao Peng, Yan Zhong, Anxin Wang
article en
10 citations

Abstract

Human cortical neural progenitor cell transplantation holds significant potential in cortical stroke treatment by replacing lost cortical neurons and repairing damaged brain circuits. However, commonly utilized human cortical neural progenitors are limited in yield a substantial proportion of diverse cortical neurons and require an extended period to achieve functional maturation and synaptic integration, thereby potentially diminishing the optimal therapeutic benefits of cell transplantation for cortical stroke. Here, we generated forkhead box G1 (FOXG1)-positive forebrain progenitors from human inducible pluripotent stem cells, which can differentiate into diverse and balanced cortical neurons including upper- and deep-layer excitatory and inhibitory neurons, achieving early functional maturation simultaneously in vitro. Furthermore, these FOXG1 forebrain progenitor cells demonstrate robust cortical neuronal differentiation, rapid functional maturation and efficient synaptic integration after transplantation into the sensory cortex of stroke-injured adult rats. Notably, we have successfully utilized the non-invasive <sup>18</sup>F-SynVesT-1 PET imaging technique to assess alterations in synapse count before and after transplantation therapy of FOXG1 progenitors in vivo. Moreover, the transplanted FOXG1 progenitors improve sensory and motor function recovery following stroke. These findings provide systematic and compelling evidence for the suitability of these FOXG1 progenitors for neuronal replacement in ischemic cortical stroke.

Nature CommunicationsVol. 16(1)
Zhejiang Chinese Medical University (CN), Ministry of Education (NZ), Allen Institute for Brain Science (US), Johns Hopkins University (US), Johns Hopkins Medicine (US), Westlake University (CN), Zhejiang Cancer Hospital (CN), Zhejiang Lab (CN), Zhejiang Academy of Medical Sciences (CN), Cancer Hospital of Chinese Academy of Medical Sciences (CN), Yebio Bioengineering (China) (CN), Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine (CN), National Institutes of Health Clinical Center (US), Second Affiliated Hospital of Zhejiang University (CN), Huashan Hospital (CN), Hangzhou Cancer Hospital (CN), Zhejiang University (CN)
National Natural Science Foundation of China, Natural Science Foundation of Zhejiang Province
Zero hunger
Openalex Percentile: Top 1%
Neurogenesis and neuroplasticity mechanisms
13.19
DOIOpen Access PDFOpenAlex
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