Oligodendrocyte-like Cells Research Articles

Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells.

Cellular heterogeneity presents an important challenge to the development of cell-based therapies where there is a fundamental requirement for predictable and reproducible outcomes. Transplanted Dental Pulp Stem/Progenitor Cells (DPSCs) have demonstrated early promise in experimental models of spinal cord injury and stroke, despite limited evidence of neuronal and glial-like differentiation after transplantation. Here, we report, for the first time, on the ability of single cell-derived clonal cultures of murine DPSCs to differentiate in vitro into immature neuronal-like and oligodendrocyte-like cells. Importantly, only DPSC clones with high nestin mRNA expression levels were found to successfully differentiate into Map2 and NF-positive neuronal-like cells. Neuronally differentiated DPSCs possessed a membrane capacitance comparable with primary cultured striatal neurons and small inward voltage-activated K+ but not outward Na+ currents were recorded suggesting a functionally immature phenotype. Similarly, only high nestin-expressing clones demonstrated the ability to adopt Olig1, Olig2, and MBP-positive immature oligodendrocyte-like phenotype. Together, these results demonstrate that appropriate markers may be used to provide an early indication of the suitability of a cell population for purposes where differentiation into a specific lineage may be beneficial and highlight that further understanding of heterogeneity within mixed cellular populations is required.

Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest

SummaryGlioblastoma (GBM) is an aggressive brain tumor whose growth is driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stem cells (GSCs) and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Here we find only a subset of GSC cultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns. Chromatin accessibility mapping identified loci that failed to alter in response to BMP and these were enriched in SOX transcription factor-binding motifs. SOX transcription factors, therefore, may limit differentiation commitment. A similar propensity for cell-cycle re-entry and de-differentiation was observed in GSC-derived oligodendrocyte-like cells. These findings highlight significant obstacles to BMP-induced differentiation as therapy for GBM.

Electroacupuncture Promotes the Differentiation of Transplanted Bone Marrow Mesenchymal Stem Cells Preinduced With Neurotrophin-3 and Retinoic Acid Into Oligodendrocyte-Like Cells in Demyelinated Spinal Cord of Rats.

Transplantation of bone marrow mesenchymal stem cells (MSCs) promotes functional recovery in multiple sclerosis (MS) patients and in a murine model of MS. However, there is only a modicum of information on differentiation of grafted MSCs into oligodendrocyte-like cells in MS. The purpose of this study was to transplant neurotrophin-3 (NT-3) and retinoic acid (RA) preinduced MSCs (NR-MSCs) into a demyelinated spinal cord induced by ethidium bromide and to investigate whether EA treatment could promote NT-3 secretion in the demyelinated spinal cord. We also sought to determine whether increased NT-3 could further enhance NR-MSCs overexpressing the tyrosine receptor kinase C (TrkC) to differentiate into more oligodendrocyte-like cells, resulting in increased remyelination and nerve conduction in the spinal cord. Our results showed that NT-3 and RA increased transcription of TrkC mRNA in cultured MSCs. EA increased NT-3 levels and promoted differentiation of oligodendrocyte-like cells from grafted NR-MSCs in the demyelinated spinal cord. There was evidence of myelin formation by grafted NR-MSCs. In addition, NR-MSC transplantation combined with EA treatment (the NR-MSCs + EA group) reduced demyelination and promoted remyelination. Furthermore, the conduction of cortical motor-evoked potentials has improved compared to controls. Together, our data suggest that preinduced MSC transplantation combined with EA treatment not only increased MSC differentiation into oligodendrocyte-like cells forming myelin sheaths, but also promoted remyelination and functional improvement of nerve conduction in the demyelinated spinal cord.

Combination of electroacupuncture and grafted mesenchymal stem cells overexpressing TrkC improves remyelination and function in demyelinated spinal cord of rats.

This study attempted to graft neurotrophin-3 (NT-3) receptor (TrkC) gene modified mesenchymal stem cells (TrkC-MSCs) into the demyelinated spinal cord and to investigate whether electroacupuncture (EA) treatment could promote NT-3 secretion in the demyelinated spinal cord as well as further enhance grafted TrkC-MSCs to differentiate into oligodendrocytes, remyelination and functional recovery. Ethidium bromide (EB) was microinjected into the spinal cord of rats at T10 to establish a demyelinated model. Six groups of animals were prepared for the experiment: the sham, PBS, MSCs, MSCs+EA, TrkC-MSCs and TrkC-MSCs+EA groups. The results showed that TrkC-MSCs graft combined with EA treatment (TrkC-MSCs+EA group) significantly increased the number of OPCs and oligodendrocyte-like cells differentiated from MSCs. Immunoelectron microscopy showed that the oligodendrocyte-like cells differentiated from TrkC-MSCs formed myelin sheaths. Immunofluorescence histochemistry and Western blot analysis indicated that TrkC-MSCs+EA treatment could promote the myelin basic protein (MBP) expression and Kv1.2 arrangement trending towards the normal level. Furthermore, behavioural test and cortical motor evoked potentials detection demonstrated a significant functional recovery in the TrkC-MSCs+EA group. In conclusion, our results suggest that EA treatment can increase NT-3 expression, promote oligodendrocyte-like cell differentiation from TrkC-MSCs, remyelination and functional improvement of demyelinated spinal cord.

Elevated in vivo levels of a single transcription factor directly convert satellite glia into oligodendrocyte-like cells.

Oligodendrocytes are the myelinating glia of the central nervous system and ensure rapid saltatory conduction. Shortage or loss of these cells leads to severe malfunctions as observed in human leukodystrophies and multiple sclerosis, and their replenishment by reprogramming or cell conversion strategies is an important research aim. Using a transgenic approach we increased levels of the transcription factor Sox10 throughout the mouse embryo and thereby prompted Fabp7-positive glial cells in dorsal root ganglia of the peripheral nervous system to convert into cells with oligodendrocyte characteristics including myelin gene expression. These rarely studied and poorly characterized satellite glia did not go through a classic oligodendrocyte precursor cell stage. Instead, Sox10 directly induced key elements of the regulatory network of differentiating oligodendrocytes, including Olig2, Olig1, Nkx2.2 and Myrf. An upstream enhancer mediated the direct induction of the Olig2 gene. Unlike Sox10, Olig2 was not capable of generating oligodendrocyte-like cells in dorsal root ganglia. Our findings provide proof-of-concept that Sox10 can convert conducive cells into oligodendrocyte-like cells in vivo and delineates options for future therapeutic strategies.

3. Dysembryoplastic neuroepithelial tumourlike neoplasm of the septum pellucidum: a case report

<h3>Background</h3> Dysembryoplastic Neuroepithelial Tumour-like Neoplasm of the Septum Pellucidum is a rare, low grade CNS neoplasm that may be misdiagnosed as a diffuse glioma. <h3>Clinical features</h3> We report a case of a 22 year old woman who presented with a first seizure. She was found to have a 31 mm non-enhancing cystic lesion on the right hand side of the anterior septum pellucidum. <h3>Pathological features</h3> The lesion was completely resected and the specimen was received as fragmented pale-white gelatinous pieces of tissue. Histologically the lesion demonstrated a lobular, microcystic, and mucin-rich appearance, and had relatively well defined margins. A population of small uniform cells, often with perinuclear halos, and cytologically virtually indistinguishable from oligodendroglioma predominated. These small ‘oligodendrocyte-like cells' (OLC) formed somewhat ‘patterned' architectural arrangements with perivascular pseudorosettes and laminated arrays resembling the specific glioneuronal component of a dysembryoplastic neuroepithelial tumour. Rare individual neurons ‘floating' in myxoid microcystic spaces were also present. These floating neurons lacked dysplastic features and evidence of satellitosis. Immunohistochemical staining showed mixed glioneuronal differentiation and the MIB1 proliferation index was low (less than 1%). PCR amplification and Sanger direct bidirectional sequencing for IDH1 and IDH2 mutations were negative. <h3>Discussion</h3> Less than 20 cases of this rare tumour have been reported to date. DNT-like lesions should be included in differential diagnosis of midline intraventricular tumours in children and young adults. Distinction from diffuse glioma is essential because these tumours appear to behave in a benign fashion.

Differentiation of human CD146-positive endometrial stem cells to adipogenic-, osteogenic-, neural progenitor-, and glial-like cells.

The aim of this study was to investigate the potential differentiation of CD146(+) endometrial stem cells to several lineages. Endometrial stromal cells were cultured using Dulbecco's modified Eagle's medium/Hams F-12 (DMEM/F-12) and were passaged every 7-10 d when cultures reached 80-100% of confluency. The immunophenotypes of single endometrial cells were analyzed using flow cytometry at fourth passage. Then the CD146(+) cells were sorted using magnetic-activated cell sorting, and they were cultured and analyzed for in vitro differentiation to several lineages. Detection of adipocyte- and osteocyte-like cells were assessed by oil red O and alizarin red staining, respectively. For detection of neural progenitor and oligodendrocyte-like cells, the cells were immunostained by neurofilament 68 and oligo2, respectively. The rates of CD90, CD105, CD146, CD31, CD34, and CD9 of cultured endometrial cells were 94.98 ± 3%, 95.77 ± 2.5%, 27.61 ± 2%, 0.79 ± 0.05%, 1.43 ± 0.1%, and 1.01 ± 0.06%, respectively. CD146(+) cells were isolated to high purity. CD146(+)-differentiated cells to adipogenic cell with typical lipid-rich vacuoles and osteogenic cells were observed and confirmed their mesenchymal origin. They also differentiated into neural progenitor and glial differentiation by retinoic acid, basic fibroblast growth factor, and epidermal growth factor signaling molecules, respectively, and confirmed by neurofilament 68 and oligo2 immunocytochemistry. The efficiency of differentiation to neural progenitor and oligodendrocyte-like cells was 90 ± 3.4% and 79 ± 2.8%, respectively. This study showed that CD146(+) cells from human endometrium after in vitro cultivation can differentiate into adipogenic-, osteogenic-, neural progenitor-, and glial-like cells. They may provide available alternative source of stem cells for future cell-based therapies and tissue engineering applications.

Improvement of spinal contusion model by cotransplanting bone marrow stromal cells and induced BMSCs into oligodendrocytes-like cells.

Demyelination is a common lesion in spinal cord injury, cell therapy is one of the approaches for replacing the lost oligodendrocytes. In this study, bone marrow stromal cells (BMSCs) have been transdifferentiated into oligodendrocyte-like cells (OLCs) and used in cytotherapy of contused spinal cords in rats. The BMSCs were collected from the rat long bones, and cultured and characterized by different markers, then they were preinduced with dimethyl sulfoxide followed by retinoic acid, and then the preinduced cells were induced with combination of basic fibroblast growth factor, platelet-derived growth factor and heregulin, followed by triiodothyronine. The OLCs were transplanted in the contused spinal cords of the rats, combined with undifferentiated BMSCs. Specific markers were used in order to characterize the cells by immunohistochemistry and real-time polymerase chain reaction. The BMSCs showed typical immnuoreactivity to the markers, and the OLCs were immunostained with specific markers. There was an improvement in the Basso, Beattie and Bresnahan score with reduction in the cavitation in the contused rats treated with OLCs combined with BMSCs. The transplanted cells were detected in the contused spinal cord. The combination of the transdifferentiated BMSCs into OLCs with the undifferentiated BMSCs improved the contused spinal cord.

Differentiation of neurosphere-derived rat neural stem cells into oligodendrocyte-like cells by repressing PDGF-α and Olig2 with triiodothyronine.

One of the approaches for treating demyelination diseases is cytotherapy, and adult stem cells are potential sources. In this investigation, we tried to increase the yield of oligodendrocyte-like cells (OLCs) by inducing neural stem cells generated from BMSCs-derived neurospheres, which were used for deriving the neural stem cells (NSCs). The latter were induced into OLCs by heregulin, PDGF-AA, bFGF and triiodothyronine (T3). The BMSCs, NS, NSCs and OLCs were characterized by using immunocytochemistry for fibronectin, CD44, CD90, CD45, Oct-4, O4, Olig2, O1 and MBP markers. PDGF receptor α (PDGFR-α), Olig2 and MOG expression were evaluated by RT-PCR. The BMSCs expressed CD44, CD90, CD106 and Oct-4; the NSCs were immunoreactive to nestin and neurofilament 68. Incubation of the NSCs for 4 days with heregulin, PDGF-AA and bFGF resulted in their induction into oligodendrocyte progenitor-like cells (OPLCs), which immunoreacted to O4, Olig2 and O1, while Olig2 and PDGFR-α were detected by RT-PCR. Replacing heregulin, PDGF-AA and bFGF with T3 for 6 days resulted in repression of O4, O1, Olig2 and PDGFR-α. The OLCs were co-cultured with motoneurons resulted in induction of MOG and MBP, which were expressed in functional OLCs. The latter can be generated from BMSCs-derive NS with high yield.

Electro-acupuncture promotes the survival and differentiation of transplanted bone marrow mesenchymal stem cells pre-induced with neurotrophin-3 and retinoic acid in gelatin sponge scaffold after rat spinal cord transection.

In the past decades, mesenchymal stem cells (MSCs) as a promising cell candidate have received the most attention in the treatment of spinal cord injury (SCI). However, due to the low survival rate and low neural differentiation rate, the grafted MSCs do not perform well as one would have expected. In the present study, we tested a combinational therapy to improve on this situation. MSCs were loaded into three-dimensional gelatin sponge (GS) scaffold. After 7days of induction with neurotrophin-3 (NT-3) and retinoic acid (RA) in vitro, we observed a significant increase in TrkC mRNA transcription by Real-time PCR and this was confirmed by in situ hybridization. The expression of TrkC was also confirmed by Western blot and immunohistochemistry. Differentiation potential of MSCs in vitro into neuron-like cells or oligodendrocyte-like cells was further demonstrated by using immunofluorescence staining. The pre-induced MSCs seeding in GS scaffolds were then grafted into the transected rat spinal cord. One day after grafting, Governor Vessel electro-acupuncture (GV-EA) treatment was applied to rats in the NR-MSCs + EA group. At 30days after GV-EA treatment, it found that the grafted MSCs have better survival rate and neuron-like cell differentiation compared with those without GV-EA treatment. The sustained TrkC expression in the grafted MSCs as well as increased NT-3 content in the injury/graft site by GV-EA suggests that NT-3/TrkC signaling pathway may be involved in the promoting effect. This study demonstrates that GV-EA and pre-induction with NT-3 and RA together may promote the survival and differentiation of grafted MSCs in GS scaffold in rat SCI.

Reconditioning effect of oligodendrocyte-like cell transplantation in acute spinal cord injury in rats

To observe the reconditioning effect of oligodendrocyte-like cell transplantation in acute spinal cord injury in rats, bone marrow mesenchymal stem cells were differentiated into oligodendrocyte-like cells induced by cytokines including insulin-like growth factor-1(IGF-1). Rats with acute spinal cord injury were treated with the oligodendrocyte-like cells for 8 weeks by local injection. The therapeutic effect was compared with oligodendrocytes transplantation and saline. Regeneration of axon myelin sheath and functional recovery of hind limbs were significantly improved after transplantation with oligodendrocyte-like cells than that with saline. But there was no significant difference between rats treated with oligodendrocyte-like cells and oligodendrocytes. Bone marrow mesenchymal stem cells differentiating into oligodendrocyte-like cells can be induced by cytokines including IGF-1, with similar specific surface markers of oligodendrocytes. These cells can survive in injury sites of the spinal cord for a long duration after transplantation to improve recovery of neural function and reduce cavity area at injury site after acute spinal injury in rats. The possible mechanism may be regeneration of axon myelin sheath, which is helpful for reconstruction of neural reflex function. Key words: Oligodendrocyte-like cells, differentiation, spinal cord injury, transplantation.

Bone marrow stromal cell transdifferentiation into oligodendrocyte-like cells using triiodothyronine as a inducer with expression of platelet-derived growth factor α as a maturity marker.

The present study investigated the functional maturity of oligodendrocyte derived from rat bone marrow stromal cells (BMSC). The BMSC were isolated from female Sprague-Dawley rats and evaluated for different markers, such as fibronectin, CD106, CD90, Oct-4 and CD45. Transdifferentiation of OLC from BMSC was obtained by exposing the BMSC to DMSO and 1 µM all-trans-retinoic acid during the pre-induction stage and then induced by heregulin (HRG), platelet-derived growth factor AA (PDGFR-alpha), fibroblast growth factor and T3. The neuroprogenitor cells (NPC) were evaluated for nestin, neurofilament 68, neurofilament 160 and glial fibrillary acidic protein gene expression using immunocytochemistry. The OLC were assessed by immunocytochemistry for O4, oligo2, O1 and MBP marker and gene expression of PDGFR-alpha was examined by RT-PCR. Our results showed that the fibronectin, CD106, CD90, CD45 and Oct-4 were expressed after the fourth passage. Also, the yield of OLC differentiation was about 71% when using the O1, O4 and oligo2 markers. Likewise, the expression of PDGFR-alpha in pre-oligodendrocytes was noticed, while MBP expression was detected in oligodendrocyte after 6 days of the induction. The conclusion of the study showed that BMSC can be induced to transdifferentiate into mature OLC.

Oligodendroglioma (WHO grade I) in a young epilepsy patient: A specific entity lying within the spectrum of dysembryoplastic neuroepithelial tumor?

We studied a frontal lobe subcortical cystic tumor that had been resected from a 13-year-old girl with a 3-year history of intractable partial seizure. Currently, more than 13 years after surgery, the patient remains recurrence-free and has no neurological deficits. Histological examination showed that the tumor was non-infiltrating and paucicellular with a mucinous matrix, and consisted of fairly uniform small cells with round to oval nuclei. Within the mucinous matrix, the tumor cells were often arranged in pseudorosettes around small blood vessels. Mitotic activity and necrosis were absent, with a Ki-67 labeling index of <1%. Based on the immunohistochemical and ultrastructural findings, the constituent tumor cells were considered to be those of oligodendroglioma, including mini-gemistocytes and gliofibrillary oligodendrocytes. No neuronal elements were identified. Features of cortical dysplasia (FCD Type 1) were evident in the cortex covering the lesion. The surrounding white matter also contained a significant number of ectopic neurons. The entire pathological picture appeared to differ somewhat from that of ordinary oligodendroglioma (WHO grade II). Considering the clinical and pathological features, the present unusual oligodendroglioma appeared to represent a previously undescribed form of oligodendroglioma (WHO grade I) lying within the spectrum of dysembryoplastic neuroepithelial tumor (DNT; WHO grade I). Simultaneously, the present oligodendroglioma also raises the question of whether or not oligodendrocyte-like cells of DNTs truly show neurocytic differentiation.

Expression of Vitamin D Receptor and Metabolizing Enzymes in Multiple Sclerosis—Affected Brain Tissue

Vitamin D deficiency has been implicated as a risk factor for multiple sclerosis (MS), but how vitamin D metabolism affects MS pathophysiology is not understood. We studied the expression of vitamin D receptor (VDR) and related enzymes, including 1,25(OH)(2)D-24-hydroxylase (24-OHase; CYP24A1) and 25(OH)D-1α-hydroxylase (CYP27B1), in CNS tissues of 39 MS patients and 20 controls and in primary human glial cells in vitro. In control and MS normal-appearing white matter (NAWM), nuclear VDR immunostaining was observed in oligodendrocyte-like cells, human leukocyte antigen (HLA)-positive microglia, and glial fibrillary acidic protein-positive astrocytes. There was a 2-fold increase in VDR transcripts in MS NAWM versus control white matter (p = 0.03). In chronic active MS lesions, HLA-positive microglia/macrophages showed nuclear VDR staining; astrocytes showed nuclear and cytoplasmic VDR staining. Staining for 24-OHase was restricted to astrocytes.VDR and CYP27B1 mRNA expressions were increased in active MS lesions versus NAWM (p < 0.01, p = 0.04, respectively). In primary human astrocytes in vitro, the active form of vitamin D, 1,25(OH)(2)D(3), induced upregulation of VDR and CYP24A1. Tumor necrosis factor and interferon-γ upregulated CYP27B1 mRNA in primary human microglia and astrocytes. Increased VDR expression in MS NAWM and inflammatory cytokine-induced amplified expression of VDR and CYP27B1 in chronic active MS lesions suggest increased sensitivity to vitamin D in NAWM and a possible endogenous role for vitamin D metabolism in the suppression of active MS lesions.

Effects of Erythropoietin in Murine-Induced Pluripotent Cell-Derived Panneural Progenitor Cells

Induced cell fate changes by reprogramming of somatic cells offers an efficient strategy to generate autologous pluripotent stem (iPS) cells from any adult cell type. The potential of iPS cells to differentiate into various cell types is well established, however the efficiency to produce functional neurons from iPS cells remains modest. Here, we generated panneural progenitor cells (pNPCs) from mouse iPS cells and investigated the effect of the neurotrophic growth factor erythropoietin (EPO) on their survival, proliferation and neurodifferentiation. Under neural differentiation conditions, iPS-derived pNPCs gave rise to microtubule-associated protein-2 positive neuronlike cells (34% to 43%) and platelet-derived growth factor receptor positive oligodendrocytelike cells (21% to 25%) while less than 1% of the cells expressed the astrocytic marker glial fibrillary acidic protein. Neuronlike cells generated action potentials and developed active presynaptic terminals. The pNPCs expressed EPO receptor (EPOR) mRNA and displayed functional EPOR signaling. In proliferating cultures, EPO (0.1-3 U/mL) slightly improved pNPC survival but reduced cell proliferation and neurosphere formation in a concentration-dependent manner. In differentiating cultures EPO facilitated neurodifferentiation as assessed by the increased number of β-III-tubulin positive neurons. Our results show that EPO inhibits iPS pNPC self-renewal and promotes neurogenesis.

Clinicopathologic analysis of dysembryoplastic neuroepithelial tumor

To study the clinicopathologic features, radiologic findings, treatment options and prognosis of dysembryoplastic neuroepithelial tumor (DNT). The clinicopathologic and radiologic features were retrospectively analyzed in 10 cases of DNT. Intractable partial seizure was the main presenting symptom in all patients. The tumor was located in temporal lobe (number = 5), frontal lobe (number = 3) or parietal lobe (number = 2). CT scan displayed a hypodense lesion. MRI scan revealed the tumor was non-enhancing T1WI hypointense and T2WI hyperintense, with internal septation and hyperintense ring around the tumor seen on FLAIR image. There was neither peritumoral edema nor mass effect. Histologically, the tumor showed the presence of glioneuronal element, with oligodendrocyte-like cells, floating neurons, astrocytes and associated microcystic changes. Immunohistochemical study demonstrated positivity for NeuN and synaptophysin in the neurons and some oligodendrocyte-like cells. Olig2 and S-100 protein were also expressed in the oligodendrocyte-like cells. Ki-67 index were lower than 1% in all cases. Nine cases were treated by complete surgical excision and the remaining case was subtotally excised. No post-operative chemotherapy or radiotherapy was given. One of the 10 cases recurred on follow up. Correct diagnosis of DNT requires correlation with clinicopathologic, radiologic and immunohistochemical findings. Complete resection of the tumor and epileptogenic foci is the mainstay of treatment for DNT, with intraoperative EEG monitoring. Post-operative chemotherapy or radiotherapy is not required.

Malignant Dysembryoplastic Neuroepithelial Tumour in a Zebrafish (Danio rerio)

Neuroectodermal tumours in man, including medulloblastoma, medulloepithelioma, neuroblastoma, esthesioneuroblastoma, primitive neuroectodermal tumour and dysembryoplastic neuroepithelial tumour, typically occur in children and young adults. These tumour types are occasionally observed in juvenile and adult zebrafish (Danio rerio) either as induced tumours in carcinogen-exposed zebrafish or as an incidental finding in zebrafish≥2years of age. An adult zebrafish submitted for routine histological examination was sent for a second opinion consultation after an uncharacteristic brain mass was identified. Microscopically, the expansile and infiltrative extracortical mass arising from the cerebellum had a diffuse microcystic pattern with solid hypercellular regions occupying 80% of the extrameningeal space and effacing the endomeninx and significantly displacing the metencephalon. The mass was composed of dense sheets of oligodendrocyte-like cells, random neurons and pseudocysts containing 'floating neurons' within a scant mucinous matrix. Neoplastic cells demonstrated positive perinuclear and intracytoplasmic expression of S-100. Malignant dysembryoplastic neuroepithelial tumour was diagnosed based on the histological features of the brain mass, which were indistinguishable from the human tumour. To our knowledge, this is the first report of a dysembryoplastic neuroepithelial tumour in a zebrafish.

In Vitro Differentiation of Bone Marrow Stromal Cells into Oligodendrocyte-like Cells Using Triiodothyronine as Inducer

ABSTRACTAn in vitro technique was devised to induced autologous adult stem cells into oligodendrocyte-like cells. In this study, a protocol was developed for the induction of bone marrow stromal cells (BMSCs) into oligodendrocyte-like cells. BMSCs were incubated in one of these three pre-inducers: dimethyl sulfoxide (DMSO), β-mercaptoethanol (βME) or biotylated hydroxyanisol (BHA), each followed by retinoic acid (RA) treatment. The percentage of viable cells in BHA-RA preinduced cells was significantly lower than the others. The results showed that the preinduced cells were immunoreactive for nestin and NF-68; among the mentioned protocols, the immunoreactivity yielded by following the DMSO-RA protocol was significantly higher than the others. Moreover, no significant immunoreactivity was observed for preinduced cells to O4, O1, MBP (myelin basic protein), S100, and GFAP (glial fibrillary acidic protein). The cells were immunoreactive to oligo-2. Two phases of induction were done: the first was a combination of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and heregulin (HRG), followed by either triiodothyronine (T3) or Forskolin (FSK) as the second phase. The conclusion is that the trans-differentiation of BMSCs by DMSO followed by RA (preinduction stage) then bFGF-PDGF-HRG followed by T3 (10 ng/ml) (induction stage) can be a potential source for oligodendrocyte-like cells preparation.

Complex Form Variant of Dysembryoplastic Neuroepithelial Tumor of the Cerebellum

Dysembryoplastic neuroepithelial tumor (DNT) is a benign neoplasm with typical supratentorial location, but the possibility of these rare tumors can also be located in the posterior fossa must be taken into account. We report a 21-year-old woman that suffered gait instability, headache, and diplopia. On CT-scan, an intraparenchymatous cerebellar tumor was disclosed. It was isodense, showing light enhancement after contrast administration. On MRI (T1-weighted image) the tumor was isointense, showing inhomogeneous hyperintensity after-gadolinium administration. On T2-weighted MRI, the tumor was inhomogenously hyperintense. At surgery, a solid and hypervascularized tumor was completely removed. Two years after surgery, the patient is symptom-free. Pathological study showed coexistence of areas of pilocytic astrocytoma with areas in which small rounded oligodendrocyte-like cells (OLC), with strong synaptophysin expression were identified. These neurocytic areas showed an eosinophilic matrix forming microcysts, and cells with aspect of “floating neurons” were occasionally identified. A complex form variant of DNT was diagnosed. Our case suggests that in presence of a cerebellar tumor with features of pilocytic astrocytoma, the possibility of a complex form variant of DNT should be considered.

Dysembryoplastic neuroepithelial tumor-like neoplasm of the septum pellucidum: review of 2 cases with chromosome 1p/19q and IDH1 analysis

Dysembryoplastic neuroepithelial tumor (DNT)-like neoplasms of the septum pellucidum are extremely rare. We reviewed 2 cases of DNT-like neoplasm of the septum pellucidum and specifically studied the immunohistochemical features and chromosomes 1p and 19q deletions. One case was a 26-year-old woman who complained of aggravated headache for 2 weeks. The other case was a 31-year-old female presenting with double vision for a month. Histological examinations showed that the lesions were composed of uniform oligodendrocytelike cells (OLCs) with obvious floating neurons in a mucin-rich background. Immunohistochemical studies revealed that both tumors were diffusely positive for Synaptophysin and Olig2. Sporadic neurons were clearly positive for NeuN. Loss of chromosome 1p/19q and isocitrate dehydrogenase 1(IDH1) mutations were not identified in both cases. It might indicate that these OLCs of DNT-like neoplasms were genetically different from glial tumors, although they showed close morphological similarities.