Induced neural stem cells from Macaca fascicularis show potential of dopaminergic neuron specification and efficacy in a mouse Parkinson's disease model

Fengyan Li; Aixia Zhang; Mo Li; Xueyao Wang; Xuan Wang; Yunqian Guan; Jing An; Deqiang Han; Y Alex Zhang; Zhiguo Chen

doi:10.1016/j.acthis.2022.151927

Induced neural stem cells from Macaca fascicularis show potential of dopaminergic neuron specification and efficacy in a mouse Parkinson's disease model

Acta Histochem. 2022 Aug;124(6):151927. doi: 10.1016/j.acthis.2022.151927. Epub 2022 Jul 2.

Authors

Fengyan Li¹, Aixia Zhang², Mo Li¹, Xueyao Wang¹, Xuan Wang¹, Yunqian Guan¹, Jing An³, Deqiang Han¹, Y Alex Zhang⁴, Zhiguo Chen⁵

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 100053, China; Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing 100069, China; Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing 100069, China.
² 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 100053, China; College of Life Sciences, Jiaying University, Meizhou, Guangdong Province 514015, China.
³ 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 100053, China.
⁴ 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 100053, China. Electronic address: yaz@bjsap.org.
⁵ 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 100053, China; Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing 100069, China; Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing 100069, China. Electronic address: chenzhiguo@gmail.com.

PMID: 35792494
DOI: 10.1016/j.acthis.2022.151927

Abstract

Induced neural stem cells (iNSCs) can be reprogrammed from somatic cells and have shown potentials in treatment of various neurological diseases/disorders. Obtaining iNSCs of nonhuman primates serves as an important bridge for clinical translation using iNSCs. In the current study, cynomolgus (Macaca fascicularis) bone marrow mesenchymal stromal cells (MSCs) were reprogrammed into iNSCs by transduction of non-integrative Sendai virus encoding transgenes OCT4, SOX2, KLF4 and C-MYC. The obtained iNSCs showed characteristics of normal neural stem cells (NSCs) and could differentiate into neurons, astrocytes and oligodendrocytes. Furthermore, iNSCs could give rise to dopaminergic neural cells in vitro, which showed safety and efficacy after transplantation into the striatum of an immunodeficient mouse Parkinson's disease (PD) model.

Keywords: Induced neural stem cells; Macaca fascicularis; Parkinson’s disease; Transplantation.

MeSH terms

Animals
Cell Differentiation
Disease Models, Animal
Dopaminergic Neurons
Macaca fascicularis
Mice
Neural Stem Cells*
Parkinson Disease* / genetics
Parkinson Disease* / therapy