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Single-Factor SOX2 Mediates Direct Neural Reprogramming of Human Mesenchymal Stem Cells via Transfection of In Vitro Transcribed mRNA

Neural stem cells (NSCs) are a prominent cell source for understanding neural pathogenesis and for developing therapeutic applications to treat neurodegenerative disease because of their regenerative capacity and multipotency. Recently, a variety of cellular reprogramming technologies have been deve...

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Autores principales: Kim, Bo-Eun, Choi, Soon Won, Shin, Ji-Hee, Kim, Jae-Jun, Kang, Insung, Lee, Byung-Chul, Lee, Jin Young, Kook, Myoung Geun, Kang, Kyung-Sun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158546/
https://www.ncbi.nlm.nih.gov/pubmed/29909688
http://dx.doi.org/10.1177/0963689718771885
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author Kim, Bo-Eun
Choi, Soon Won
Shin, Ji-Hee
Kim, Jae-Jun
Kang, Insung
Lee, Byung-Chul
Lee, Jin Young
Kook, Myoung Geun
Kang, Kyung-Sun
author_facet Kim, Bo-Eun
Choi, Soon Won
Shin, Ji-Hee
Kim, Jae-Jun
Kang, Insung
Lee, Byung-Chul
Lee, Jin Young
Kook, Myoung Geun
Kang, Kyung-Sun
author_sort Kim, Bo-Eun
collection PubMed
description Neural stem cells (NSCs) are a prominent cell source for understanding neural pathogenesis and for developing therapeutic applications to treat neurodegenerative disease because of their regenerative capacity and multipotency. Recently, a variety of cellular reprogramming technologies have been developed to facilitate in vitro generation of NSCs, called induced NSCs (iNSCs). However, the genetic safety aspects of established virus-based reprogramming methods have been considered, and non-integrating reprogramming methods have been developed. Reprogramming with in vitro transcribed (IVT) mRNA is one of the genetically safe reprogramming methods because exogenous mRNA temporally exists in the cell and is not integrated into the chromosome. Here, we successfully generated expandable iNSCs from human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via transfection with IVT mRNA encoding SOX2 (SOX2 mRNA) with properly optimized conditions. We confirmed that generated human UCB-MSC-derived iNSCs (UM-iNSCs) possess characteristics of NSCs, including multipotency and self-renewal capacity. Additionally, we transfected human dermal fibroblasts (HDFs) with SOX2 mRNA. Compared with human embryonic stem cell-derived NSCs, HDFs transfected with SOX2 mRNA exhibited neural reprogramming with similar morphologies and NSC-enriched mRNA levels, but they showed limited proliferation ability. Our results demonstrated that human UCB-MSCs can be used for direct reprogramming into NSCs through transfection with IVT mRNA encoding a single factor, which provides an integration-free reprogramming tool for future therapeutic application.
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spelling pubmed-61585462018-10-01 Single-Factor SOX2 Mediates Direct Neural Reprogramming of Human Mesenchymal Stem Cells via Transfection of In Vitro Transcribed mRNA Kim, Bo-Eun Choi, Soon Won Shin, Ji-Hee Kim, Jae-Jun Kang, Insung Lee, Byung-Chul Lee, Jin Young Kook, Myoung Geun Kang, Kyung-Sun Cell Transplant Original Articles Neural stem cells (NSCs) are a prominent cell source for understanding neural pathogenesis and for developing therapeutic applications to treat neurodegenerative disease because of their regenerative capacity and multipotency. Recently, a variety of cellular reprogramming technologies have been developed to facilitate in vitro generation of NSCs, called induced NSCs (iNSCs). However, the genetic safety aspects of established virus-based reprogramming methods have been considered, and non-integrating reprogramming methods have been developed. Reprogramming with in vitro transcribed (IVT) mRNA is one of the genetically safe reprogramming methods because exogenous mRNA temporally exists in the cell and is not integrated into the chromosome. Here, we successfully generated expandable iNSCs from human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via transfection with IVT mRNA encoding SOX2 (SOX2 mRNA) with properly optimized conditions. We confirmed that generated human UCB-MSC-derived iNSCs (UM-iNSCs) possess characteristics of NSCs, including multipotency and self-renewal capacity. Additionally, we transfected human dermal fibroblasts (HDFs) with SOX2 mRNA. Compared with human embryonic stem cell-derived NSCs, HDFs transfected with SOX2 mRNA exhibited neural reprogramming with similar morphologies and NSC-enriched mRNA levels, but they showed limited proliferation ability. Our results demonstrated that human UCB-MSCs can be used for direct reprogramming into NSCs through transfection with IVT mRNA encoding a single factor, which provides an integration-free reprogramming tool for future therapeutic application. SAGE Publications 2018-06-18 2018-07 /pmc/articles/PMC6158546/ /pubmed/29909688 http://dx.doi.org/10.1177/0963689718771885 Text en © The Author(s) 2018 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Articles
Kim, Bo-Eun
Choi, Soon Won
Shin, Ji-Hee
Kim, Jae-Jun
Kang, Insung
Lee, Byung-Chul
Lee, Jin Young
Kook, Myoung Geun
Kang, Kyung-Sun
Single-Factor SOX2 Mediates Direct Neural Reprogramming of Human Mesenchymal Stem Cells via Transfection of In Vitro Transcribed mRNA
title Single-Factor SOX2 Mediates Direct Neural Reprogramming of Human Mesenchymal Stem Cells via Transfection of In Vitro Transcribed mRNA
title_full Single-Factor SOX2 Mediates Direct Neural Reprogramming of Human Mesenchymal Stem Cells via Transfection of In Vitro Transcribed mRNA
title_fullStr Single-Factor SOX2 Mediates Direct Neural Reprogramming of Human Mesenchymal Stem Cells via Transfection of In Vitro Transcribed mRNA
title_full_unstemmed Single-Factor SOX2 Mediates Direct Neural Reprogramming of Human Mesenchymal Stem Cells via Transfection of In Vitro Transcribed mRNA
title_short Single-Factor SOX2 Mediates Direct Neural Reprogramming of Human Mesenchymal Stem Cells via Transfection of In Vitro Transcribed mRNA
title_sort single-factor sox2 mediates direct neural reprogramming of human mesenchymal stem cells via transfection of in vitro transcribed mrna
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158546/
https://www.ncbi.nlm.nih.gov/pubmed/29909688
http://dx.doi.org/10.1177/0963689718771885
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