A ROCK Inhibitor Blocks the Inhibitory Effect of Chondroitin Sulfate Proteoglycan on Morphological Changes of Mesenchymal Stromal/Stem Cells into Neuron-Like Cells
Biomolecules & Therapeutics
;
: 447-453, 2013.
Article
in English
| WPRIM
| ID: wpr-202595
ABSTRACT
Chondroitin sulfate proteoglycan (CSPG) inhibits neurite outgrowth of various neuronal cell types, and CSPG-associated inhibition of neurite outgrowth is mediated by the Rho/ROCK pathway. Mesenchymal stromal/stem cells (MSCs) have the potential to differentiate into neuron-like cells under specific conditions and have been shown to differentiate into neuron-like cells by co-treatment with the ROCK inhibitor Y27632 and the hypoxia condition mimicking agent CoCl2. In this study, we addressed the hypothesis that a ROCK inhibitor might be beneficial to regenerate neurons during stem cell therapy by preventing transplanted MSCs from inhibition by CSPG in damaged tissues. Indeed, dose-dependent inhibition by CSPG pretreatment was observed during morphological changes of Wharton's jelly-derived MSCs (WJ-MSCs) induced by Y27632 alone. The formation of neurite-like structures was significantly inhibited when WJ-MSCs were pre-treated with CSPG before induction under Y27632 plus CoCl2 conditions, and pretreatment with a protein kinase C inhibitor reversed such inhibition. However, CSPG treatment resulted in no significant inhibition of the WJ-MSC morphological changes into neuron-like cells after initiating induction by Y27632 plus CoCl2. No marked changes were detected in expression levels of neuronal markers induced by Y27632 plus CoCl2 upon CSPG treatment. CSPG also blocked the morphological changes of human bone marrow-derived MSCs into neuron-like cells under other neuronal induction condition without the ROCK inhibitor, and Y27632 pre-treatment blocked the inhibitory effect of CSPG. These results suggest that a ROCK inhibitor can be efficiently used in stem cell therapy for neuronal induction by avoiding hindrance from CSPG.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Chondroitin Sulfate Proteoglycans
/
Stem Cells
/
Protein Kinase C
/
Chondroitin
/
Chondroitin Sulfates
/
Neurites
/
Hypoxia
/
Neurons
Limits:
Humans
Language:
English
Journal:
Biomolecules & Therapeutics
Year:
2013
Type:
Article
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