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

Authors
Kim, SS; Yoo, SW; Park, TS; Ahn, SC; Jeong, HS; Kim, JW; Chang, DY; Cho, KG; Kim, SU; Huh, Y; Lee, JE; Lee, SY; Lee, YD; Suh-Kim, H
Citation
Stem cells, 26(9):2217-2228, 2008
Journal Title
Stem cells
ISSN
0250-6793
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.
MeSH terms
AnimalsApoptosisBasic Helix-Loop-Helix Transcription Factors/biosynthesis*Brain Ischemia/complicationsBrain Ischemia/physiopathologyBrain Ischemia/therapy*Cell DifferentiationCell ProliferationCells, CulturedHumansMaleMesenchymal Stem Cell Transplantation*Mesenchymal Stem Cells/cytologyMesenchymal Stem Cells/metabolism*Mesoderm/cytologyMiceMotor ActivityNerve Tissue Proteins/biosynthesis*Neurons/cytologyNeurons/metabolism*RatsRats, Sprague-DawleyStroke/etiologyStroke/physiopathologyStroke/therapy*
DOI
10.1634/stemcells.2008-0108
PMID
18617687
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
Journal Papers > School of Medicine / Graduate School of Medicine > Neurosurgery
AJOU Authors
김, 성수유, 승완조, 경기이, 영돈서, 해영
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