Characterization of Human-Induced Neural Stem Cells and Derivatives following Transplantation into the Central Nervous System of a Nonhuman Primate and Rats

Mengjia Li; Zhengbo Wang; Tianqi Zheng; Tianzhuang Huang; Baoguo Liu; Deqiang Han; Sumei Liu; Bochao Liu; Mo Li; Wei Si; Y Alex Zhang; Yuyu Niu; Zhiguo Chen

doi:10.1155/2022/1396735

Characterization of Human-Induced Neural Stem Cells and Derivatives following Transplantation into the Central Nervous System of a Nonhuman Primate and Rats

Stem Cells Int. 2022 Dec 28:2022:1396735. doi: 10.1155/2022/1396735. eCollection 2022.

Authors

Mengjia Li¹, Zhengbo Wang², Tianqi Zheng¹, Tianzhuang Huang², Baoguo Liu^{1

3}, Deqiang Han¹, Sumei Liu¹, Bochao Liu¹, Mo Li¹, Wei Si², Y Alex Zhang^{1

4}, Yuyu Niu^{2

5}, Zhiguo Chen^{1

4

6}

Affiliations

¹ Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, And Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China.
² State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medical, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
³ College of Pharmacy, Jilin University, Changchun, Jilin 130021, China.
⁴ Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing 100069, China.
⁵ Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
⁶ Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing 100069, China.

Abstract

Neural stem cells (NSCs) and derivatives are potential cellular sources to treat neurological diseases. In the current study, we reprogrammed human peripheral blood mononuclear cells into induced NSCs (iNSCs) and inserted GFP gene into the AAVS1 site for graft tracing. Targeted integration of GFP does not affect the proliferation and differentiation capacity of iNSCs. iNSC-GFP can be further differentiated into dopaminergic precursors (DAPs) and motor neuron precursors (MNPs), respectively. iNSCs were engrafted into the motor cortex and iNSC-DAPs into the striatum and substantia nigra (SN) of a nonhuman primate, respectively. The surviving iNSCs could respond to the microenvironment of the cortex and spontaneously differentiate into mature neurons that extended neurites. iNSC-DAPs survived well and matured into DA neurons following transplantation into the striatum and SN. iNSC-MNPs could also survive and turn into motor neurons after being engrafted into the spinal cord of rats. The results suggest that iNSCs and derivatives have a potential to be used for the treatment of neurological diseases.