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Stem Cell Res. 2016 Mar;16(2):236-42. doi: 10.1016/j.scr.2016.01.016. Epub 2016 Jan 15.

Conversion of adult human peripheral blood mononuclear cells into induced neural stem cell by using episomal vectors.

Author information

1
Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, and Key Laboratory of Neurodegeneration, 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
Department of Neurobiology, Beijing Key Laboratory of Major Brain Disorders, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100069, China.
3
Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, and Key Laboratory of Neurodegeneration, Ministry of Education, Beijing 100053, China.
4
Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing 100069, China.
5
Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, and Key Laboratory of Neurodegeneration, Ministry of Education, Beijing 100053, China; Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing 100069, China. Electronic address: yaz@bjsap.org.
6
Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, and Key Laboratory of Neurodegeneration, 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.

Abstract

Human neural stem cells (NSCs) hold great promise for research and therapy in neural diseases. Many studies have shown direct induction of NSCs from human fibroblasts, which require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Peripheral blood (PB) is routinely used in medical diagnoses, and represents a noninvasive and easily accessible source of cells. Here we show direct derivation of NSCs from adult human PB mononuclear cells (PB-MNCs) by employing episomal vectors for transgene delivery. These induced NSCs (iNSCs) can expand more than 60 passages, can exhibit NSC morphology, gene expression, differentiation potential, and self-renewing capability and can give rise to multiple functional neural subtypes and glial cells in vitro. Furthermore, the iNSCs carry a specific regional identity and have electrophysiological activity upon differentiation. Our findings provide an easily accessible approach for generating human iNSCs which will facilitate disease modeling, drug screening, and possibly regenerative medicine.

KEYWORDS:

Episomal vectors; Human peripheral blood mononuclear cells; Induced neural stem cells

PMID:
26826927
DOI:
10.1016/j.scr.2016.01.016
[Indexed for MEDLINE]
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