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Overexpression of microRNA-124 promotes the neuronal differentiation of bone marrow-derived mesenchymal stem cells

neural Regeneration Research 2014年第12期9卷 1241-1248页

作者： Defeng Zou Yi Chen Yaxin Han Chen Lv Guanjun Tu Department of Orthopedics First Affiliated Hospital of China Medical University Department of Orthopedics Jinhua Central Hospital of Zhejiang University

microRNAs （miRNAs） play an important regulatory role in the self-renewal and differentiation of stem cells. In this study, we examined the effects of miRNA-124 （miR-124） overexpression in bone marrow-derived mesenchymal stem cells. In particular, we focused on the effect of overexpression on the differentiation of bone marrow-derived mesenchymal stem cells into neurons. First, we used GeneChip technology to analyze the expression of miRNAs in bone marrow-derived mesen- chymal stem cells, neural stem cells and neurons, miR-124 expression was substantially reduced in bone marrow-derived mesenchymal stem cells compared with the other cell types. We con- structed a lentiviral vector overexpressing miR-124 and transfected it into bone marrow-derived mesenchymal stem cells. Intracellular expression levels of the neuronal early markers [3-III tu- bulin and microtubule-associated protein-2 were significantly increased, and apoptosis induced by oxygen and glucose deprivation was reduced in transfected cells. After miR-124-transfected bone marrow-derived mesenchymal stem cells were transplanted into the injured rat spinal cord, a large number of cells positive for the neuronal marker neurofilament-200 were observed in the transplanted region. The Basso-Beattie-Bresnahan locomotion scores showed that the motor function of the hind limb of rats with spinal cord injury was substantially improved. These re- sults suggest that miR-124 plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells into neurons. Our findings should facilitate the development of novel strategies for enhancing the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation for spinal cord injury.

关键词： nerve regeneration microRNA-124 lentivirus overexpression bone marrow-de-rived mesenchymal stem cells neural stern cells spinal cord injury neurogenesis GeneChip motor function NSFC grant neural regeneration

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引用

neural Regeneration Research 2013年第25期8卷 2360-2369页

作者： Guanqun Qiao Qingquan Li Gang Peng Jun Ma Hongwei Fan Yingbin Li Department of Neurosurgery the Second Affiliated Hospital of Nanjing Medical University Department of Pharmacology the Third Affiliated Hospital of Nanjing Medical University

Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models （c-myc/SV40Tag＋/Tet-on＋） to explore the malignant trans- formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cells were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibrillary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibrillary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibrillary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cells. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

关键词： neural regeneration stem cells neural stern cells brain tumor stem cells subventricular zone braintumor transgenic mouse model multidirectional differentiation doxycycline neuroregeneration

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Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injury

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neural Regeneration Research 2014年第24期9卷 2197-2204页

作者： Zhi Li Wei Zhao Wei Liu Ye Zhou Jingqiao Jia Lifeng Yang Department of Orthopedics Affiliated Central Hospital of Shenyang Medical College Department of Obstetrics Affiliated Central Hospital of Shenyang Medical College Liaoning Province Wellcare Stem cells Biotechnology Co. Ltd.

Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the field of nerve damage repair. In the present study, human placenta-derived mesenchymal stem ceils were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the restoration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.

关键词： nerve regeneration stem cells placenta-derived mesenchymal stem cells spinal cord injury neural stern cells nerve-like cells motor function sensory function neural regeneration

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