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Neural transdifferentiation of human bone marrow mesenchymal stem cells on hydrophobic polymer-modified surface and therapeutic effects in an animal model of ischemic stroke

 J.S. Heo  ;  S.-M. Choi  ;  H.O. Kim  ;  E.H. Kim  ;  J. You  ;  T. Park  ;  E. Kim  ;  H.-S. Kim 
 NEUROSCIENCE, Vol.238 : 305-318, 2013 
Journal Title
Issue Date
Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/physiology* ; Brain Ischemia/physiopathology ; Brain Ischemia/therapy* ; Cell Adhesion/physiology ; Cell Transdifferentiation/physiology* ; Disease Models, Animal ; Humans ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/physiology* ; Motor Activity/physiology ; Neurogenesis/physiology* ; Neurons/physiology ; Rats ; Recovery of Function/physiology ; Stroke/physiopathology ; Stroke/therapy*
bone marrow ; DTOPV ; differentiation ; MSC ; neural stem cells ; neurosphere
Human bone marrow-derived mesenchymal stem cells (MSCs) have multi-lineage differentiation potential and can become cells of mesodermal and neural lineages. These stem cells thus hold considerable clinical promise for the treatment of neurodegenerative diseases. For successful regeneration of damaged neural tissues, directed differentiation of neural or neuronal precursor cells from MSCs and integration of transplanted cells are pivotal factors. We induced MSCs into neurogenesis using a modified protocol. The therapeutic potency of the resulting neural progenitor cells in a rat model of ischemic stroke was analyzed. Using a highly hydrophobic diphenylamino-s-triazine-bridged p-phenylene (DTOPV)-coated surface and adopting a procedure for propagation of neural stem cells, we efficiently converted MSCs into neurosphere-like cellular aggregates (NS-MSCs). The spherical cells were subsequently induced to differentiate into neural cells expressing neuroectodermal markers. To determine whether these cells had neuronal fates and induced neuro-protective effects in vivo, NS-MSCs were intra-cerebrally administered to rats 48 h after permanent middle cerebral artery occlusion (pMCAo). The results showed a remarkable attenuation of ischemic damage with significant functional recovery, although the cells were not fully incorporated into the damaged tissues on post-operative day 26. Improvement in the NS-MSC-transplanted rats was faster than in the MSC group and suppression of inflammation was likely the key factor. Thus, our culture system using the hydrophobic surface of a biocompatible DTOPV coating efficiently supported neural cell differentiation from MSCs. Neural-primed MSCs exhibited stronger therapeutic effects than MSCs in rat brains with pMCAo.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kim, E. H.(김은해)
Kim, Han Soo(김한수)
Kim, Hyun Ok(김현옥) ORCID logo https://orcid.org/0000-0002-4964-1963
Choi, Seong Mi(최성미)
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