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Neural induction with neurogenin1 increases the therapeutic effects of mesenchymal stem cells in the ischemic brain.

Authors
 SUNG-SOO KIM  ;  SEUNG-WAN YOO  ;  TAE-SEOK PARK  ;  SEUNG-CHEOL AHN  ;  HAN-SEONG JEONG  ;  JI-WON KIM  ;  DA-YOUNG CHANG  ;  KYUNG-GI CHO  ;  SEUNG U. KIM  ;  YOUNGBUHM HUH  ;  JONG-EUN LEE  ;  SOO-YEOL LEE  ;  YOUNG-DON LEE  ;  HAEYOUNG SUH-KIM 
Citation
 STEM CELLS, Vol.26(9) : 2217-2228, 2008 
Journal Title
STEM CELLS
ISSN
 1066-5099 
Issue Date
2008
MeSH
Animals ; Apoptosis ; Basic Helix-Loop-Helix Transcription Factors/biosynthesis* ; Brain Ischemia/complications ; Brain Ischemia/physiopathology ; Brain Ischemia/therapy* ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Humans ; Male ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism* ; Mesoderm/cytology ; Mice ; Motor Activity ; Nerve Tissue Proteins/biosynthesis* ; Neurons/cytology ; Neurons/metabolism* ; Rats ; Rats, Sprague-Dawley ; Stroke/etiology ; Stroke/physiopathology ; Stroke/therapy*
Keywords
Animals ; Apoptosis ; Basic Helix-Loop-Helix Transcription Factors/biosynthesis* ; Brain Ischemia/complications ; Brain Ischemia/physiopathology ; Brain Ischemia/therapy* ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Humans ; Male ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism* ; Mesoderm/cytology ; Mice ; Motor Activity ; Nerve Tissue Proteins/biosynthesis* ; Neurons/cytology ; Neurons/metabolism* ; Rats ; Rats, Sprague-Dawley ; Stroke/etiology ; Stroke/physiopathology ; Stroke/therapy*
Abstract
Mesenchymal stem cells (MSCs) have been shown to ameliorate a variety of neurological dysfunctions. This effect is believed to be mediated by their paracrine functions, since these cells rarely differentiate into neuronal cells. It is of clinical interest whether neural induction of MSCs is beneficial for the replacement therapy of neurological diseases. Here we report that expression of Neurogenin1 (Ngn1), a proneural gene that directs neuronal differentiation of progenitor cells during development, is sufficient to convert the mesodermal cell fate of MSCs into a neuronal one. Ngn1-expressing MSCs expressed neuron-specific proteins, including NeuroD and voltage-gated Ca2+ and Na+ channels that were absent in parental MSCs. Most importantly, transplantation of Ngn1-expressing MSCs in the animal stroke model dramatically improved motor functions compared with the parental MSCs. MSCs with Ngn1 populated the ischemic brain, where they expressed mature neuronal markers, including microtubule associated protein 2, neurofilament 200, and vesicular glutamate transporter 2, and functionally connected to host neurons. MSCs with and without Ngn1 were indistinguishable in reducing the numbers of Iba1+, ED1+ inflammatory cells, and terminal deoxynucleotidyl transferase dUTP nick-end labeling(+) apoptotic cells and in increasing the numbers of proliferating Ki67+ cells. The data indicate that in addition to the intrinsic paracrine functions of MSCs, motor dysfunctions were remarkably improved by MSCs able to transdifferentiate into neuronal cells. Thus, neural induction of MSCs is advantageous for the treatment of neurological dysfunctions.
Files in This Item:
T200801629.pdf Download
DOI
10.1634/stemcells.2008-0108
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107965
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