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Directed Induction of Functional Motor Neuron-Like Cells from Genetically Engineered Human Mesenchymal Stem Cellsopen access

Authors
Park, Hwan-WooCho, Jung-SunPark, Chul-KyuJung, Sung JunPark, Chang-HwanLee, Shin-JaeOh, Seog BaePark, Young-SeokChang, Mi-Sook
Issue Date
Apr-2012
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.7, no.4, pp.1 - 12
Indexed
SCIE
SCOPUS
Journal Title
PLOS ONE
Volume
7
Number
4
Start Page
1
End Page
12
URI
https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/165973
DOI
10.1371/journal.pone.0035244
ISSN
1932-6203
Abstract
Cell replacement using stem cells is a promising therapeutic approach to treat degenerative motor neuron (MN) disorders, such as amyotrophic lateral sclerosis and spinal cord injury. Human bone marrow-derived mesenchymal stem cells (hMSCs) are a desirable cell source for autologous cell replacement therapy to treat nervous system injury due to their plasticity, low immunogenicity, and a lower risk of tumor formation than embryonic stem cells. However, hMSCs are inefficient with regards to differentiating into MN-like cells. To solve this limitation, we genetically engineered hMSCs to express MN-associated transcription factors, Olig2 and Hb9, and then treat the hMSCs expressing Olig2 and Hb9 with optimal MN induction medium (MNIM). This method of induction led to higher expression (>30% of total cells) of MN markers. Electrophysiological data revealed that the induced hMSCs had the excitable properties of neurons and were able to form functional connections with muscle fibers in vitro. Furthermore, when the induced hMSCs were transplanted into an injured organotypic rat spinal cord slice culture, an ex vivo model of spinal cord injury, they exhibited characteristics of MNs. The data strongly suggest that induced Olig2/Hb9-expressing hMSCs were clearly reprogrammed and directed toward a MN-like lineage. We propose that methods to induce Olig2 and Hb9, followed by further induction with MNIM have therapeutic potential for autologous cell replacement therapy to treat degenerative MN disorders.
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서울 의생명공학전문대학원 > 서울 의생명과학과 > 1. Journal Articles
서울 의과대학 > 서울 생리학교실 > 1. Journal Articles

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