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논문 기본 정보

자료유형
학술저널
저자정보
Lim, Hee-Suk (Cancer Research Institute and Department of Medical Lifescience, College of Medicine, The Catholic University of Korea) Joe, Young Ae (Cancer Research Institute and Department of Medical Lifescience, College of Medicine, The Catholic University of Korea)
저널정보
한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제21권 제6호
발행연도
2013.1
수록면
447 - 453 (7page)

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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 $CoCl_2$. 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 $CoCl_2$ 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 $CoCl_2$. No marked changes were detected in expression levels of neuronal markers induced by Y27632 plus $CoCl_2$ 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.
#Mesenchymal stromal/stem cell #ROCK inhibitor #Chondroitin sulfate proteoglycan #PKC inhibitor #Y27632

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참고문헌 (30)

참고문헌 신청
Can, A. / 2007 / Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells / Stem Cells 25:2886~2895 google schola Chen, M. S. / 2000 / Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1 / Nature 403:434~439 google schola Choi, M. / 2013 / Proangiogenic features of Wharton's jelly-derived mesenchymal stromal/stem cells and their ability to form functional vessels / Int. J. Biochem. Cell Biol 45:560~570 google schola Datta, I. / 2011 / Neuronal plasticity of human Wharton's jelly mesenchymal stromal cells to the dopaminergic cell type compared with human bone marrow mesenchymal stromal cells / Cytotherapy 13:918~932 google schola Dergham, P. / 2002 / Rho signaling pathway targeted to promote spinal cord repair / J. Neurosci 22:6570~6577 google schola

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