Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (7): 3103-3113.doi: 10.4103/NRR.NRR-D-24-01176

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Generation of humanized spinal astrocytic chimeric rat spinal cord model by engrafting human dorsal spinal neural stem/progenitor cells

Wenjie Xu1, 2, #, Ziyu He1, 2, #, Jia Xu2, 3, 4, Ruoying Zhang1, 2, Shu Fan1, 2, Zhixian Liu1, 2, Wei Wang1, 2, 5, Hong Chen2, 3, 4, *, Xiaolong Zheng1, 2, 5, *   

  1. 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; 
    2Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; 
    3Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; 
    4Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; 
    5Key Laboratory of Neurological Diseases of Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • Online:2026-07-15 Published:2026-04-01
  • Contact: Hong Chen, MD, PhD, chenhong1129@hust.edu.cn; Xiaolong Zheng, PhD, xl_zheng@hust.edu.cn.
  • Supported by:
    This study was supported by the Ministry of Science and Technology of China (STI2030-Major Projects), No. 2022ZD0204700 (to WW); the National Natural Science Foundation of China, No. 82301572 (to XZ); and the China Postdoctoral Science Foundation, No. 2023M731202 (to XZ).

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Abstract: In the human spinal cord, astrocytes are the major glial cells. In vitro studies of human astrocytes are relatively simple. However, the straightforward nature of the in vitro environment and complex nature of the in vivo environment limit comprehensive investigations into the structure and function of human astrocytes. Additionally, in vivo studies of human astrocytes are further limited by ethical issues. This means there is an urgent need to develop effective in vivo models to study the structure and function of human astrocytes. Here, we first directed human embryonic stem cells to differentiate into human spinal cord dorsal neural stem/progenitor cells in vitro, before transplanting these cells into the gray matter of the cervical spinal cord (C5–T2 segments) of naïve nude rats to create a chimeric human astrocytic rat spinal cord model. The transplanted human spinal cord dorsal neural stem/ progenitor cells survived for at least 20 months in the spinal cord environment of the rats, with over 90% differentiating into human astrocytes. These human astrocytes were able to migrate caudally for long distances along the white matter towards the spinal cord. They expressed astrocytic cytoskeletal proteins and functionally-related proteins, suggesting their maturation and structural integration into the rat spinal cord. Thus, this humanized astrocyte chimeric rat spinal cord model provides a valuable tool for studying the role of human spinal cord astrocytes in various spinal diseases. 

Key words: chimeric, dorsal spinal neural stem/progenitor cells, human embryonic stem cells, human spinal astrocytes, long-term, migration, spinal cord