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05 December 2012, Volume 7 Issue 34 Previous Issue    Next Issue

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Differentiation of rhesus adipose stem cells into dopaminergic neurons Yan Zhou, Maosheng Sun, Hongjun Li, Min Yan, Tianhong Xie 2012, 7 (34):  2645-2652.  doi: 10.3969/j.issn.1673-5374.2012.34.001 Abstract ( 599 )   PDF (339KB) ( 1134 )   Save LIM homeobox transcription factor 1a (Lmx1a) has the capacity to initiate the development program of neuronal cells and promote the differentiation of embryonic stem cells into dopaminergic neurons. In this study, rhesus adipose stem cells were infected with recombinant adenovirus carrying the Lmx1a gene and co-cultured with embryonic rat neural stem cells. Cell differentiation was induced using sonic hedgehog and fibroblast growth factor-8. Immunofluorescence staining showed that cells were positive for neuron-specific enolase and β-tubulin III. Reverse transcription-PCR results demonstrated that rhesus adipose stem cells were not only positive for neuron-specific enolase and β-tubulin III, but also positive for the dopaminergic neuron marker, tyrosine hydroxylase, neurofilament, glial cell line-derived neurotrophic factor family receptor α2 and nuclear receptor related factor 1. The number of Lmx1a gene-infected cells expressing the dopaminergic neuron marker was substantially greater than the number of cells not infected with Lmx1α gene. These results suggest that Lmx1a-mediated regulation combined with the strategy of co-culture with neural stem cells can robustly promote the differentiation of rhesus adipose stem cells into dopaminergic neurons. References | Related Articles | Metrics

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Bone marrow-derived mesenchymal stem cells increase dopamine synthesis in the injured striatum Yue Huang, Cheng Chang, Jiewen Zhang, Xiaoqun Gao 2012, 7 (34):  2653-2662.  doi: 10.3969/j.issn.1673-5374.2012.34.002 Abstract ( 316 )   PDF (338KB) ( 907 )   Save Previous studies showed that tyrosine hydroxylase or neurturin gene-modified cells transplanted into rats with Parkinson’s disease significantly improved behavior and increased striatal dopamine content. In the present study, we transplanted tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells into the damaged striatum of Parkinson’s disease model rats. Several weeks after cell transplantation, in addition to an improvement of motor function, tyrosine hydroxylase and neurturin proteins were up-regulated in the injured striatum, and importantly, levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid increased significantly. Furthermore, the density of the D2 dopamine receptor in the postsynaptic membranes of dopaminergic neurons was decreased. These results indicate that transplantation of tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells increases dopamine synthesis and significantly improves the behavior of rats with Parkinson’s disease. References | Related Articles | Metrics

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Umbilical cord-derived mesenchymal stem cells retain immunomodulatory and anti-oxidative activities after neural induction Jianjun Li, Dong Li, Xiuli Ju, Qing Shi, Dakun Wang, Fengcai Wei 2012, 7 (34):  2663-2672.  doi: 10.3969/j.issn.1673-5374.2012.34.003 Abstract ( 315 )   PDF (280KB) ( 958 )   Save The immunomodulatory and anti-oxidative activities of differentiated mesenchymal stem cells contribute to their therapeutic efficacy in cell-replacement therapy. Mesenchymal stem cells were isolated from human umbilical cord and induced to differentiate with basic fibroblast growth factor, nerve growth factor, epidermal growth factor, brain-derived neurotrophic factor and forskolin. The mesenchymal stem cells became rounded with long processes and expressed the neural markers, Tuj1, neurofilament 200, microtubule-associated protein-2 and neuron-specific enolase. Nestin expression was significantly reduced after neural induction. The expression of immunoregulatory and anti-oxidative genes was largely unchanged prior to and after neural induction in mesenchymal stem cells. There was no significant difference in the effects of control and induced mesenchymal stem cells on lymphocyte proliferation in co-culture experiments. However, the expression of human leukocyte antigen-G decreased significantly in induced neuron-like cells. These results suggest that growth factor-based methods enable the differentiation of mesenchymal stem cell toward immature neuronal-like cells, which retain their immunomodulatory and anti-oxidative activities. References | Related Articles | Metrics

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Neuronal-like differentiation of bone marrow-derived mesenchymal stem cells induced by striatal extracts from a rat model of Parkinson’s disease Xiaoling Qin, Wang Han, Zhigang Yu 2012, 7 (34):  2673-2680.  doi: 10.3969/j.issn.1673-5374.2012.34.004 Abstract ( 245 )   PDF (210KB) ( 871 )   Save A rat model of Parkinson’s disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from the femur and tibia, and were co-cultured with 10% and 60% lesioned or intact striatal extracts. The results showed that when exposed to lesioned striatal extracts, BMSCs developed bipolar or multi-polar morphologies, and there was an increase in the percentage of cells that expressed glial fibrillary acidic protein (GFAP), nestin and neuron-specific enolase (NSE). Moreover, the percentage of NSE-positive cells increased with increasing concentrations of lesioned striatal extracts. However, intact striatal extracts only increased the percentage of GFAP-positive cells. The findings suggest that striatal extracts from Parkinson’s disease rats induce BMSCs to differentiate into neuronal-like cells in vitro. References | Related Articles | Metrics

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Use of FK506 and bone marrow mesenchymal stem cells for rat hind limb allografts Youxin Song, Zhujun Wang, Zhixue Wang, Hong Zhang, Xiaohui Li, Bin Chen 2012, 7 (34):  2681-2688.  doi: 10.3969/j.issn.1673-5374.2012.34.005 Abstract ( 225 )   PDF (208KB) ( 1002 )   Save Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance. bone marrow mesenchymal stem cells were intramuscularly (gluteus maximus) injected with FK506 (tacrolimus) daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 + bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 + bone marrow mesenchymal stem cells group. The FK506 + bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant. References | Related Articles | Metrics

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Neural cell injury microenvironment induces neural differentiation of human umbilical cord mesenchymal stem cells Jin Zhou, Guoping Tian, Jinge Wang, Xiaoguang Luo, Siyang Zhang, Jianping Li, Li Li, Bing Xu, Feng Zhu, Xia Wang, Chunhong Jia, Weijin Zhao, Danyang Zhao, Aihua Xu 2012, 7 (34):  2689-2697.  doi: 10.3969/j.issn.1673-5374.2012.34.006 Abstract ( 295 )   PDF (287KB) ( 971 )   Save This study aimed to investigate the neural differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs) under the induction of injured neural cells. After in vitro isolation and culture, passage 5 hUCMSCs were used for experimentation. hUCMSCs were co-cultured with normal or Aβ1-40-injured PC12 cells, PC12 cell supernatant or PC12 cell lysate in a Transwell co-culture system. Western blot analysis and flow cytometry results showed that choline acetyltransferase and microtubule-associated protein 2, a specific marker for neural cells, were expressed in hUCMSCs under various culture conditions, and highest expression was observed in the hUCMSCs co-cultured with injured PC12 cells. Choline acetyltransferase and microtubule-associated protein 2 were not expressed in hUCMSCs cultured alone (no treatment). Cell Counting Kit-8 assay results showed that hUCMSCs under co-culture conditions promoted the proliferation of injured PC12 cells. These findings suggest that the microenvironment during neural tissue injury can effectively induce neural cell differentiation of hUCMSCs. These differentiated hUCMSCs likely accelerate the repair of injured neural cells. References | Related Articles | Metrics

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Ipsilateral versus bilateral limb-training in promoting the proliferation and differentiation of endogenous neural stem cells following cerebral infarction in  rats Xiyao Yang, Feng Zhu, Xiaomei Zhang, Zhuo Gao, Yunpeng Cao 2012, 7 (34):  2698-2704.  doi: 10.3969/j.issn.1673-5374.2012.34.007 Abstract ( 201 )   PDF (232KB) ( 848 )   Save We investigated the effects of ipsilateral versus bilateral limb-training on promotion of endogenous neural stem cells in the peripheral infarct zone and the corresponding cerebral region in the unaffected hemisphere of rats with cerebral infarction. Middle cerebral artery occlusion was induced in Wistar rats. The rat forelimb on the unaffected side was either wrapped up with tape to force the use of the paretic forelimb in rats or not braked to allow bilateral forelimbs to participate in training. Daily training consisted of mesh drum training, balance beam training, and stick rolling training for a total of 40 minutes, once per day. Control rats received no training. At 14 days after functional training, rats receiving bilateral limb-training exhibited milder neurological impairment than that in the ipsilateral limb-training group or the control group. The number of nestin/glial fibrillary acidic protein-positive and nestin/microtubule-associated protein 2-positive cells in the peripheral infarct zone and in the corresponding cerebral region in the unaffected hemisphere was significantly higher in rats receiving bilateral limb-training than in rats receiving ipsilateral limb-training. These data suggest that bilateral limb-training can promote the proliferation and differentiation of endogenous neural stem cells in the bilateral hemispheres after cerebral infarction and accelerate the recovery of neurologic function. In addition, bilateral limb-training produces better therapeutic effects than ipsilateral limb-training. References | Related Articles | Metrics

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Tolerance of neurite outgrowth to Rho kinase inhibitors decreased by cyclooxygenase-2  inhibitor Weigang Duan, Ling Que, Xiaoman Lv, Qifeng Li, Hua Yin, Luyong Zhang 2012, 7 (34):  2705-2712.  doi: 10.3969/j.issn.1673-5374.2012.34.008 Abstract ( 311 )   PDF (248KB) ( 1191 )   Save In this study, PC12 Adh cells and Neuro-2a cells were treated with Rho-associated kinase inhibitors (Y27632 and Fasudil), a cyclooxygenase-1 selective inhibitor (SC560), and a cyclooxygenase-2 inhibitor (NS398). We found that these cells became tolerant to Rho-associated kinase inhibitors, as neurite outgrowth induced by these inhibitors diminished following more than 3 days of exposure in either cell line. The proteins cyclooxygenase-2 and cytosolic prostaglandin E synthetase were upregulated at day 3. NS398 decreased the tolerance to neurite outgrowth induction in both cell lines, whereas SC560 had almost no effect. These findings indicate that cells become tolerant to neurite outgrowth induced by Rho-associated kinase inhibitors, this is at least partly associated with upregulation of proteins involved in the cyclooxygenase-2 pathway, and cyclooxygenases-2 inhibition prevents this tolerance. References | Related Articles | Metrics

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Binocular form deprivation influences the visual cortex Mingming Liu, Chuanhuang Weng, Hanping Xie, Wei Qin 2012, 7 (34):  2713-2718.  doi: 10.3969/j.issn.1673-5374.2012.34.009 Abstract ( 341 )   PDF (124KB) ( 1047 )   Save α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are considered to play a crucial role in synaptic plasticity in the developing visual cortex. In this study, we established a rat model of binocular form deprivation by suturing the rat binocular eyelids before eye-opening at postnatal day 14. During development, the decay time of excitatory postsynaptic currents mediated by α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors of normal rats became longer after eye- opening; however, the decay time did not change significantly in binocular form deprivation rats. The peak value in the normal group became gradually larger with age, but there was no significant change in the binocular form deprivation group. These findings indicate that binocular form deprivation influences the properties of excitatory postsynaptic currents mediated by α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the rat visual cortex around the end of the critical period, indicating that form stimulation is associated with the experience-dependent modification of neuronal synapses in the visual cortex. References | Related Articles | Metrics

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Lysine-specific demethylase 1 expression in zebrafish during the early stages of neuronal development Aihong Li, Yong Sun, Changming Dou, Jixian Chen, Jie Zhang 2012, 7 (34):  2719-2726.  doi: 10.3969/j.issn.1673-5374.2012.34.010 Abstract ( 272 )   PDF (277KB) ( 986 )   Save Lysine-specific demethylase 1 (Lsd1) is associated with transcriptional coregulation via the modulation of histone methylation. The expression pattern and function of zebrafish Lsd1 has not, however, been studied. Here, we describe the pattern of zebrafish Lsd1 expression during different development stages. In the zebrafish embryo, lsd1 mRNA was present during the early cleavage stage, indicating that maternally derived Lsd1 protein is involved in embryonic patterning. During embryogenesis from 0 to 48 hours post-fertilization (hpf), the expression of lsd1 mRNA in the embryo was ubiquitous before 12 hpf and then became restricted to the anterior of the embryo (particularly in the brain) from 24 hpf to 72 hpf. Inhibition of Lsd1 activity (by exposure to tranylcypromine) or knockdown of lsd1 expression (by morpholino antisense oligonucleotide injection) led to the loss of cells in the brain and to a dramatic downregulation of neural genes, including gad65, gad75, and reelin, but not hey1. These findings indicate an important role of Lsd1 during nervous system development in zebrafish. References | Related Articles | Metrics

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Research progress in hepatic encephalopathy in recent 10 years A Web of Science-based literature analysis Nan Li 2012, 7 (34):  2727-2733.  doi: 10.3969/j.issn.1673-5374.2012.34.011 Abstract ( 370 )   PDF (109KB) ( 1087 )   Save Abstract OBJECTIVE: To analyze international research trends in hepatic encephalopathy and examine the role of neuroelectrophysiology and neuroimaging in diagnosis of hepatic encephalopathy. DATA RETRIEVAL: We performed a bibliometric analysis of studies on hepatic encephalopathy published during 2002–2011 retrieved from Web of Science. SELECTION CRITERIA: Inclusion criteria: (1) peer-reviewed published articles on hepatic encephalopathy; (2) original article, review, meeting abstract, proceedings paper, book chapter, editorial material, news items, and (3) published during 2002–2011. Exclusion criteria: (1) articles that required manual searching or telephone access; (2) documents that were not published in the public domain; and (3) corrected papers from the total number of articles. MAIN OUTCOME MEASURES: (1) Annual publication output; (2) type of publication; (3) publication by research field; (4) publication by journal; (5) publication by author; (6) publication by institution; (7) publication by country; (8) publication by institution in China; (9) most-cited papers.  RESULTS: A total of 3 233 papers regarding hepatic encephalopathy were retrieved during 2002–2011. The number of papers gradually increased over the 10-year study period and was highest in 2010. Most papers appeared in journals with a focus on gastroenterology and hepatology. Among the included journals, Hepatology published the greatest number of papers regarding hepatic encephalopathy, and the published studies were highly cited. Thus, Hepatology appears to represent a key journal publishing papers on hepatic encephalopathy. Regarding distribution by country for publications on hepatic encephalopathy indexed in Web of Science during 2002–2011, the United States published highest number of papers, with China ranked ninth. As per distribution by institute for publications, the University of Montreal in Canada published the highest number of papers (n = 111). Among the Chinese institutes, Zhejiang University in China was the most prolific institute with 15 papers. CONCLUSION: The present bibliometric analysis on hepatic encephalopathy provides an overview of research progress, as well as identifying the most active institutes and experts in this research field during 2002–2011. Research into hepatic encephalopathy has revealed changes in neural injury and regeneration in hepatic encephalopathy. Neuroelectrophysiological and neuroimaging examinations are important for determining clinical classifications and disease severity of hepatic encephalopathy, providing a foundation for further research. References | Related Articles | Metrics

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Follicle and melanocyte stem cells, and their application in neuroscience A Web of Science-based literature analysis Weifu Wu 2012, 7 (34):  2734-2741.  doi: 10.3969/j.issn.1673-5374.2012.34.012 Abstract ( 399 )   PDF (70KB) ( 858 )   Save OBJECTIVE: To identify global research trends of follicle and melanocyte stem cells, and their application in neuroscience. DATA RETRIEVAL: We performed a bibliometric analysis of studies from 2002 to 2011 on follicle and melanocyte stem cells, and their application in neuroscience, which were retrieved from the Web of Science, using the key words follicle stem cell or melanocyte stem cell, and neural, neuro or nerve. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on follicle and melanocyte stem cells, and their application in neuroscience, which were indexed in the Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) a number of corrected papers from the total number of articles. MAIN OUTCOME MEASURES: (1) Distribution of publications on follicle and melanocyte stem cells by years, journals, countries, institutions, institutions in China, and most cited papers. (2) Distribution of publications on the application of follicle and melanocyte stem cells in neuroscience by years, journals, countries, institutions, and most cited papers. RESULTS: Of the 348 publications from 2002 to 2011 on follicle and melanocyte stem cells, which were retrieved from the Web of Science, more than half were from American authors and institutes. The most prolific institutions in China for publication of papers on follicle and melanocyte stem cells were the Fourth Military Medical University and Third Military Medical University. The most prolific journals for publication of papers on follicle and melanocyte stem cells were the Journal of Investigative Dermatology, Pigment Cell & Melanoma Research. Of the 63 publications from 2002 to 2011 on the application of follicle and melanocyte stem cells in neuroscience, which were retrieved from the Web of Science, more than half were from American authors and institutes, and no papers were from Chinese authors and institutes. The most prolific journals for publication of papers on the application of follicle and melanocyte stem cells in neuroscience were the Journal of Investigative Dermatology, Pigment Cell & Melanoma Research. CONCLUSION: Based on our analysis of the literature and research trends, we found that follicle stem cells might offer further benefits in neural regenerative medicine. References | Related Articles | Metrics