mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells

Phil Jun Kang; Daryeon Son; Tae Hee Ko; Wonjun Hong; Wonjin Yun; Jihoon Jang; Jong-Il Choi; Gwonhwa Song; Jangbo Lee; In Yong Kim; Seungkwon You

doi:10.3390/cells8091043

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mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells

Journal article

Open access

Peer reviewed

mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells

Phil Jun Kang, Daryeon Son, Tae Hee Ko, Wonjun Hong, Wonjin Yun, Jihoon Jang, Jong-Il Choi, Gwonhwa Song, Jangbo Lee, In Yong Kim, …

Cells (Basel, Switzerland), Vol.8(9), p.1043

09/06/2019

DOI: 10.3390/cells8091043

PMCID: PMC6769943

PMID: 31489945

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Abstract

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner.

Adult

Animals

Cells, Cultured

Cellular Reprogramming

Cellular Reprogramming Techniques - methods

Female

Humans

Male

Mice

Mice, Inbred BALB C

Mice, Nude

Neural Stem Cells - cytology

Neural Stem Cells - metabolism

RNA, Messenger - genetics

RNA, Messenger - metabolism

Transgenes

Urine - cytology

Details

Title: Subtitle: mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells
Creators: Phil Jun Kang - Korea University
Daryeon Son - Korea University
Tae Hee Ko - Korea University Medical Center
Wonjun Hong - Korea University
Wonjin Yun - Korea University
Jihoon Jang - University of Seoul
Jong-Il Choi - Korea University Medical Center
Gwonhwa Song - Korea University
Jangbo Lee - University of Seoul
In Yong Kim - Korea University
Seungkwon You - Korea University
Resource Type: Journal article
Publication Details: Cells (Basel, Switzerland), Vol.8(9), p.1043
DOI: 10.3390/cells8091043
PMID: 31489945
PMCID: PMC6769943
NLM abbreviation: Cells
ISSN: 2073-4409
eISSN: 2073-4409
Grant note: DOI: 10.13039/501100003710, name: Korea Health Industry Development Institute, award: HI18C2166; name: National Research Foundation (NRF, South Korea), award: NRF-2014M3A9D3034158, NRF-2015M3A9B4071074, NRF-2015R1D1A1A02061859
Language: English
Date published: 09/06/2019
Academic Unit: Neurosurgery
Record Identifier: 9984460341502771

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