• Journal of Embryo Transfer
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• v.32 no.2
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• pp.39-45
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• 2017

Mesenchymal stem cells (MSCs) have been considered an alternative source of neuronal lineage cells, which are difficult to isolate from brain and expand in vitro. Previous studies have reported that MSCs expressing Nestin ($Nestin^+$ MSCs), a neuronal stem/progenitor cell marker, exhibit increased transcriptional levels of neural development-related genes, indicating that $Nestin^+$ MSCs may exert potential with neurogenic differentiation. Accordingly, we investigated the effects of the presence of $Nestin^+$ MSCs in bone-marrow-derived primary cells (BMPCs) on enhanced neurogenic differentiation of BMPCs by identifying the presence of $Nestin^+$ MSCs in uncultured and cultured BMPCs. The percentage of $Nestin^+$ MSCs in BMPCs was measured per passage by double staining with Nestin and CD90, an MSC marker. The efficiency of neurogenic differentiation was compared among passages, revealing the highest and lowest yields of $Nestin^+$ MSCs. The presence of $Nestin^+$ MSCs was identified in BMPCs before in vitro culture, and the highest and lowest percentages of $Nestin^+$ MSCs in BMPCs was observed at the third (P3) and fifth passages (P5). Moreover, significantly the higher efficiency of differentiation into neurons, oligodendrocyte precursor cells and astrocytes was detected in BMPCs at P3, compared with P5. In conclusion, these results demonstrate that neurogenic differentiation can be enhanced by increasing the proportion of $Nestin^+$ MSCs in cultured BMPCs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.40 no.4
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• pp.173-180
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• 2014

Objectives: The purpose of this study was to investigate the neurogenic differentiation of human dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and stem cells from apical papilla (SCAP). Materials and Methods: After induction of neurogenic differentiation using commercial differentiation medium, expression levels of neural markers, microtubule-associated protein 2 (MAP2), class III ${\beta}$-tubulin, and glial fibrillary acidic protein (GFAP) were identified using reverse transcriptase polymerase chain reaction (PCR), real-time PCR, and immunocytochemistry. Results: The induced cells showed neuron-like morphologies, similar to axons, dendrites, and perikaryons, which are composed of neurons in DPSCs, PDLSCs, and SCAP. The mRNA levels of neuronal markers tended to increase in differentiated cells. The expression of MAP2 and ${\beta}$-tubulin III also increased at the protein level in differentiation groups, even though GFAP was not detected via immunocytochemistry. Conclusion: Human dental stem cells including DPSCs, PDLSCs, and SCAP may have neurogenic differentiation capability in vitro. The presented data support the use of human dental stem cells as a possible alternative source of stem cells for therapeutic utility in the treatment of neurological diseases.

• 대한생식의학회:학술대회논문집
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• 2006.06a
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• pp.168.2-168.2
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• 2006

• Journal of Integrative Natural Science
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• v.12 no.4
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• pp.133-141
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• 2019

Mesenchymal stem cells (MSCs) are known to differentiate into multiple lineages, making neurogenic differentiation an important target in the clinical field. In the present study, we induced the neurogenic differentiation of cells using histone deacetylase (HDAC) inhibitors and studied their mechanisms for further differentiation in vitro. We treated cells with the HDAC inhibitors, MS-275 and NaB; and found that the cells had neuron-like features such as distinct bipolar or multipolar morphologies with branched processes. The mRNA expressions encoding for NEFL, MAP2, TUJ1, OLIG2, and SYT was significantly increased following HDAC inhibitors treatment compared to without HDAC inhibitors; high protein levels of MAP2 and Tuj1 were detected by immunofluorescence staining. We examined the mechanisms of differentiation and found that the Wnt signaling pathway and downstream mitogen-activate protein kinase were involved in neurogenic differentiation of MSCs. Importantly, Wnt4, Wnt5a/b, and Wnt11 protein levels were highly increased after treatment with NaB; signals were activated through the regulation of Dvl2 and Dvl3. Interestingly, NaB treatment increased the levels of JNK and upregulated JNK phosphorylation. After MS-275 treatment, Wnt protein levels were decreased and GSK-3β was phosphorylated. In this cell, HDAC inhibitors controlled the non-canonical Wnt expression by activating JNK phosphorylation and the canonical Wnt signaling by targeting GSK-3β.

• KSBB Journal
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• v.27 no.5
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• pp.273-280
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• 2012

Graphene is a one-atom-thick sheet composed of carbon atoms only. It has a two-dimensional honeycomb structure with $sp^2$ orbital bonding, which presents some unique properties. Due to large Young's modulus, good electrical conductivity, ability to immobilize several kinds of small molecules and proteins, and biocompatibility of graphene, it has attracted interests inits ability to enhance cell growth and differentiation, followed by recent several studies. We reviewed about the osteogenic differentiation of mesenchymal stem cells, and neurogenic differentiation of neuron stem cells, and the ectodermal and mesodermal differentiation of induced pluripotent stem cells using graphene. Graphene has not only enhanced the adhesion and proliferation of mesenchymal stem cells, but also led to the faster differentiation even without any other exogenous signals. Nonetheless, graphene has some cytotoxicities in its amount-response manner, which is critical to regenerative medicine. The cytotoxicities of graphene were compared with those of grapheneoxide and carbon nanotubes.

• Korean Journal of Bronchoesophagology
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• v.9 no.1
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• pp.87-91
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• 2003

Currently gastrointestinal mesenchymal tumors are divided into three major categories: myogenic tumors(leiomyoma, leiomyosarcoma), neurogenic tumors (schwannomas) and neoplasms that belong to neither group, which are known by GIST(gastrointestinal stromal tumors). The stromal tumors are hetrogenous, so that they may show myogenic or neurogenic differentiation or both, or no differentiation at all in some patients. The best defining feature for GIST is their expression of KIT-protein(CD117). Leiomyomas are the most common mesenchymal tumor in esophagus. Esophageal GISTS are very rare in comparision to those of the stomach and intestine. Recently we experieneced one case of the esophageal GIST, so that we describe an esophageal GIST on immunohistochemical analysis. A 70 years old woman complained of dysphagia and nausea for 3 days. FGS showed a huge elevated lesion in lower esophagus 33cm distal to incisor, which was covered with normal mucosa. CT and UGI showed the intramural tumor of lower third of the esophagus. The distal esophagectomy and esophago-gastrostomy were performed. The tumor was located in lower third of esophagus and measured as $6{\times}3.7$cm in size. Immunohistochemically, it showed weakly positive CD117 and diffusely positive S-100. SMA, desmin, NES and chromogranin showed negative immune-reaction. The patient was followed for 15 month after operation. There was no recurrence.

• Molecules and Cells
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• v.38 no.4
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• pp.362-372
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• 2015

Setdb1, an H3-K9 specific histone methyltransferase, is associated with transcriptional silencing of euchromatic genes through chromatin modification. Functions of Setdb1 during development have been extensively studied in embryonic and mesenchymal stem cells as well as neurogenic progenitor cells. But the role of Sedtdb1 in myogenic differentiation remains unknown. In this study, we report that Setdb1 is required for myogenic potential of C2C12 myoblast cells through maintaining the expressions of MyoD and muscle-specific genes. We find that reduced Setdb1 expression in C2C12 myoblast cells severely delayed differentiation of C2C12 myoblast cells, whereas exogenous Setdb1 expression had little effect on. Gene expression profiling analysis using oligonucleotide microarray and RNA-Seq technologies demonstrated that depletion of Setdb1 results in downregulation of MyoD as well as the components of muscle fiber in proliferating C2C12 cells. In addition, exogenous expression of MyoD reversed transcriptional repression of MyoD promoter-driven luciferase reporter by Setdb1 shRNA and rescued myogenic differentiation of C2C12 myoblast cells depleted of endogenous Setdb1. Taken together, these results provide new insights into how levels of key myogenic regulators are maintained prior to induction of differentiation.

• Journal of Korean Neurosurgical Society
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• v.63 no.3
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• pp.358-365
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• 2020

To describe how to perform urological evaluation in children with tethered cord syndrome (TCS). Although a common manifestation of TCS is the development of neurogenic bladder in developing children, neurosurgeons often face difficulty in detecting urological problems in patients with TCS. From a urological perspective, diagnosis of TCS in developing children is further complicated due to the differentiation between neurogenic bladder dysfunctions and transient bladder dysfunctions owing to developmental problems. Due to the paucity of evidence regarding evaluation prior to and after untethering, I have shown the purpose and tools for evaluation in my own practice. This may be tailored to the types of neurogenic bladder, developmental status, and risks for deterioration. While the urodynamic study (UDS) is the gold standard test for understanding bladder function, it is not a panacea in revealing the nature of bladder dysfunction. In addition, clinicians should consider the influence of developmental processes on bladder function. Before untethering, UDS should reveal synergic urethral movement, which indicates an intact sacral reflex and lack of TCS. Postoperatively, the measurement of post-void residual urine volume is a key factor for the evaluation of spontaneous voiders. In case of elevation, fecal impaction, which is common in spinal dysraphism, should be addressed. In patients with clean intermittent catheterization, the frequency-volume chart should be monitored to assess the storage function of the bladder. Toilet training is an important sign of maturation, and its achievement should be monitored. Signs of bladder deterioration should be acknowledged, and follow-up schedule should be tailored to prevent upper urinary tract damage and also to determine an adequate timing for intervention. Neurosurgeons should be aware of urological problems related to TCS as well as urologists. Cooperation and regular discussion between the two disciplines could enhance the quality of patient care. Accumulation of experience will improve follow-up strategies.

• Archives of Plastic Surgery
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• v.33 no.2
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• pp.205-212
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• 2006

Using adipose derived stem cells(ASCs), neurogenic differentiation was induced in a mono layered culture medium containing neuronal induction agents. Cells differentiated to the neuronal cells were observed with a inverted microscope and immunofluorecent study. We made a 15 mm long defect in the sciatic nerve of 14 rats and connected a silicone tube to the defect. Then, we mixed neuronal progenitor cells differentiated from ASCs with collagen gel and grafted them to a group of rats(experimental group) and grafted only collagen gel into another group(control group). In 4 and 8 weeks after the graft, histological observation was made. According to the result, the number and diameter of myelinated axons were significantly increased in the experimental group. In addition, the nerve conduction velocity was improved more in the experimental group and neovascularity also increased. Moreover, reaction with S100 and p75 was observed in regenerated nerves in the experimental group, suggesting that the grafted cells were differentiated into supportive cells such as Schwann's cells. In conclusion, this research proved that ASCs can multiply and differentiate into neuronal cells. If they are grafted into nerve defects, the grafted cells are differ entiated into supportive cells such as Schwann's cells and thus contribute to nerve regeneration. Accordingly, the use of adipose tissue obtained easily without the limitation of donor site can be greatly helpful in treating peripheral nerve defects.

• Journal of Korean Neurosurgical Society
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• v.29 no.12
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• pp.1570-1576
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• 2000

Objective : To evaluate objectively the sites of injury in patients with posttraumatic olfactory deficits and to suggest the diagnostic procedure for evaluation of posttraumatic anosmia. Methods : Ten patients with posttraumatic olfactory dysfunction were examined by means of olfactory testing, sinoscopy, contrast filled paranasal sinus computed tomography(contrast filled PNS CT) and magnetic resonance imaging(MRI). Five normal persons without olfactory dysfunction were also evauluated. The aerodynamic patency of olfactory cleft was examined by contrast filled PNS CT. The olfactory system(oflactory bulbs, olfactory tracts, inferior frontal region, hippocampi, or temporal lobes) was investigated in detail with MRI. The difference in the size of the olfactory bulb between normal volunteers and anosmic patients was evaluated by Student's t test. Results : Contrast filled dynamic CT scan was useful method for the evaluation of dynamic patency of the olfactory cleft. Paranasal CT scan of the all anosmic patients showed dynamic reflux of contrast media in olfactory cleft on valsalva maneuver. For the largest cross-sectional area and great height, the difference in olfactory bulb size between normal volunteers and patients was statistically significant(p<0.001) in MRI study. Conclusion : Posttraumatic anosmia was completely evaluated by olfactory testing, sinoscopy, and contrast filled CT scan for differentiation between conductive type and neurogenic type. Neurogenic anosmia was confirmed by perfect localization with MRI study.