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1.
Spinal Cord ; 56(5): 487-493, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29277840

RESUMO

STUDY DESIGN: Psychometric study using retrospectively collected data. OBJECTIVES: We investigated the comparability of quantitative computed tomography (qCT) in assessing bone mineral density (BMD) with dual energy X-ray absorptiometry (DXA). We evaluated how well previously suggested normal values for spinal Hounsfield units (HU) correlated with routine DXA results in patients with chronic spinal cord injury (SCI). Furthermore, we investigated inter/intra-observer reliability of measuring HU in the spine. SETTING: Academic medical center in Tehran, Iran. METHODS: Spinal CT scans of 44 male participants with chronic SCI who had undergone DXA studies on the same day were selected. The main outcome measures were sensitivity, specificity, and area under curve (AUC) of HU at each spinal region against DXA results of areal BMD. The secondary outcome was inter/intra-observer reliability of measuring HU in the spinal column. RESULTS: We found no significant difference between qCT and DXA results (p-value = 0.237, R = 0.188). However, the two methods showed overall unfavorable comparability, with a sensitivity of 0%, 0%, and 80%, specificity of 50%, 90%, and 85%, and area under curve (AUC) of 0.27, 0.53, and 0.83 for cervical, thoracic, and lumbar spine, respectively. The best comparability was achieved at the lumbar region although not statistically significant (p-value = 0.072). Measuring HU was reliable (inter/intra-observer reliability >98%). CONCLUSIONS: This study demonstrates that currently proposed normal values result in unfavorable comparability in the cervical and thoracic regions; however, as the agreement improved at the lumbar spine, it is possible that qCT could become an indicator of bone strength with further research.


Assuntos
Absorciometria de Fóton , Densidade Óssea , Traumatismos da Medula Espinal/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Osteoporose/complicações , Osteoporose/diagnóstico por imagem , Psicometria , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Traumatismos da Medula Espinal/complicações
2.
Cell Mol Neurobiol ; 37(2): 275-289, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27107758

RESUMO

Adipose-derived stem cells (ADSC) are adult stem cells which can be induced into motor neuron-like cells (MNLC) with a preinduction-induction protocol. The purpose of this study is to generate MNLC from neural stem cells (NSC) derived from ADSC. The latter were isolated from the perinephric regions of Sprague-Dawley rats, transdifferentiated into neurospheres (NS) using B27, EGF, and bFGF. After generating NSC from the NS, they induced into MNLC by treating them with Shh and RA, then with GDNF, CNTF, BDNF, and NT-3. The ADSC lineage was evaluated by its mesodermal differentiation and was characterized by immunostaining with CD90, CD105, CD49d, CD106, CD31, CD45, and stemness genes (Oct4, Nanog, and Sox2). The NS and the NSC were evaluated by immunostaining with nestin, NF68, and Neurod1, while the MNLC were evaluated by ISLET1, Olig2, and HB9 genes. The efficiency of MNLC generation was more than 95 ± 1.4 % (mean ± SEM). The in vitro generated myotubes were innervated by the MNLC. The induced ADSC adopted multipolar motor neuron morphology, and they expressed ISLET1, Olig2, and HB9. We conclude that ADSC can be induced into motor neuron phenotype with high efficiency, associated with differential expression of the motor neuron gene. The release of MNLC synaptic vesicles was demonstrated by FM1-43, and they were immunostained with synaptophysin. This activity was correlated with the intracellular calcium ion shift and membrane depolarization upon stimulation as was demonstrated by the calcium indicator and the voltage-sensitive dye, respectively.


Assuntos
Adipócitos/fisiologia , Transdiferenciação Celular/fisiologia , Regulação da Expressão Gênica , Neurônios Motores/fisiologia , Células-Tronco Neurais/fisiologia , Tecido Adiposo/citologia , Tecido Adiposo/fisiologia , Animais , Células Cultivadas , Técnicas de Cocultura , Feminino , Neurônios Motores/citologia , Ratos , Ratos Sprague-Dawley
3.
Cytotherapy ; 17(7): 912-21, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25939801

RESUMO

BACKGROUND AIMS: Traumatic injury to the central nervous system (CNS) often causes motor dysfunctions. However, because of the CNS complexity and variability in the clinical presentations, efforts to repair damaged CNS tissue and restoring its functions are particularly demanding. On the other hand, recent progress in the regenerative therapy field have led to novel approaches for the treatment of traumatic CNS injury and renewed hopes to overcome the obstacles. It appears that the balance between neurite re-growth-inhibiting and neurite re-growth-inducing molecules determines the axonal re-growth fate. Neurotrophic factors can tilt this balance and indeed promote cell survival and axonal re-growth over neurodegeneration. One of the promising neurotrophic factors in this field is ciliary neurotrophic factor (CNTF). METHODS: We transfected rat bone marrow stromal cells with a mammalian expression vector-inserted human CNTF gene through the use of a non-viral method to prepare human CNTF-overexpressing stem cells under ex vivo conditions. We transplanted these modified cells to the rat model of spinal cord traumatic injury to explore functional recovery after contusion induction. RESULTS: Our data from immunocytochemistry and behavioral tests showed that such cells can act as a powerful potential approach to treat traumatic CNS injuries because these modified cells improved the behavioral test scores in the rat model of spinal cord injury. CONCLUSIONS: CNTF-overexpressing bone marrow stromal cells can ameliorate spinal cord traumatic injury and can be used in the treatment of traumatic CNS injuries in the near future.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Fator Neurotrófico Ciliar/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Traumatismos da Medula Espinal/terapia , Animais , Axônios/fisiologia , Células da Medula Óssea/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fator Neurotrófico Ciliar/biossíntese , Fator Neurotrófico Ciliar/genética , Contusões/terapia , Feminino , Humanos , Modelos Animais , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Medula Espinal/cirurgia , Transfecção
4.
Med J Islam Repub Iran ; 29: 198, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26157716

RESUMO

BACKGROUND: Patients with spinal cord injury (SCI) have a lower health related quality of life (HRQOL) compared to both healthy controls and the normal population. The aim of this study was to compare HRQOL between two groups of veteran and non-veteran SCI patients. METHODS: All male paraplegic non-veterans who had sustained complete SCI before 1988 and were residents of Tehran province (Iran), and a similar group of SCI veterans who consecutively participated in a health screening program were enrolled in this study. Patients fewer than 35 and older than 65 years of age were not included in this study. The participants were interviewed based on the Persian version of SF-36 questionnaire by two psychologists. Eight sub-scales and two physical and mental component summaries of the instrument were assessed. We used chi-square, odds ratio, Mann-Whitney U, independent t-test and linear regression for analysis. RESULTS: Overall, 25 veterans and 22 non-veterans were enrolled in the study. The mean age, time since injury and the presence of comorbid illnesses were not significantly different between the two groups (P>0.05). A greater number of veterans were married (p= 0.003) and employed (p= 0.047). On average, veterans had more years of formal education than non-veterans (p= 0.001). The mean (SD) bodily pain sub-scale was 72.73(31.253) for non-veterans and 49.7 (28.287) for veterans (p=0.011). Absence of comorbid illnesses was associated with a better physical component summary (p< 0.001). Employment was associated with a better mental component summary (p= 0.022). CONCLUSION: We did not find any differences in HRQOL between the two groups except for the bodily pain sub-scale. Further studies with larger sample sizes are recommended.

5.
Neurochem Res ; 39(12): 2319-33, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25205382

RESUMO

Many studies have illustrated that much of the post-traumatic degeneration of the spinal cord cells is caused by the secondary mechanism. The aim of this study is to evaluate the effect of the anti-inflammatory property of valproic acid (VPA) on injured spinal cords (SC). The rats with the contused SC received intraperitoneal single injection of VPA (150, 200, 300, 400 or 500 mg/kg) at 2, 6, 12 and 24 h post-injury. Basso-Beattie-Bresnahan (BBB) test and H-reflex evaluated the functional outcome for 12 weeks. The SC were investigated 3 months post-injury using morphometry and glial fibrillary acid protein (GFAP) expression. Reduction in cavitation, H/M ratio, BBB scores and GFAP expression in the treatment groups were significantly more than that of the untreated one (P < 0.05). The optimal improvement in the condition of the contused rats was in the ones treated at the acute phase of injury with 300 mg/kg of VPA at 12 h post-injury, they had the highest increase in BBB score and decrease in astrogliosis and axonal loss. We conclude that treating the contused rats with 300 mg/kg of VPA at 12 h post-injury improves the functional outcome and reduces the traumatized SC gliosis.


Assuntos
Proteína Glial Fibrilar Ácida/metabolismo , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Ácido Valproico/uso terapêutico , Animais , Barreira Hematoencefálica , Ratos , Medula Espinal/fisiologia , Traumatismos da Medula Espinal/fisiopatologia
6.
Transl Neurosci ; 15(1): 20220343, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38979518

RESUMO

Spinal cord injury (SCI) is a severe medical condition that affects millions of people worldwide each year. In Iran, an estimated 9 out of every 100,000 individuals experience traumatic SCI occurrences. Long-term disabilities and comorbidities stemming from SCI often necessitate multiple therapeutic interventions. The aim of this study is to evaluate the morbidity in Iranian SCI patients. In this study, a four-step process was used to select, extract, analyze, and synthesize relevant literature. The search covered 750 records from five databases, resulting in 25 articles included in the review. These articles, published between 2000 and 2023, utilized cross-sectional, qualitative, or cohort designs. The findings explored the prevalence, risk factors, and consequences of comorbidities associated with SCI, categorized into four themes: physical, sexual, psychological, and metabolic morbidity. Physical morbidity refers to medical conditions or complications affecting body functions or structures in SCI patients. The most frequently reported cases include pressure ulcers, pain, osteoporosis, fractures, impaired pulmonary function, renal failure, and obesity. Metabolic morbidity includes conditions such as vitamin D deficiency and cardiometabolic risk factors. Psychological morbidity encompasses depression, anxiety, and adjustment disorders. Sexual morbidity refers to conditions or complications affecting the sexual function or satisfaction of SCI patients. This narrative literature review offers a comprehensive examination of various aspects of SCI in Iranian patients. The review identifies numerous challenges and difficulties faced by SCI patients while also highlighting protective factors that can improve their well-being. Additionally, the review acknowledges gaps and limitations within the current literature and suggests possible avenues for future research.

7.
Cytotherapy ; 15(9): 1073-85, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23806239

RESUMO

BACKGROUND AIMS: Cell therapy is considered a promising option for treatment of spinal cord injury (SCI). The purpose of this study is to use combined therapy of bone marrow stromal cells (BMSCs) and BMSC-derived gamma-aminobutyric acid (GABA)ergic inhibitory neurotransmitter cells (BDGCs) for the contusion model of SCI in rats. METHODS: BDGCs were prepared from BMSCs by pre-inducing them with ß-mercaptoethanol followed by retinoic acid and then inducing them by creatine. They were immunostained with BMSC, proneuronal, neural and GABA markers. The BDGCs were intraspinally transplanted into the contused rats, whereas the BMSCs were delivered intravenously. The animals were sacrificed after 12 weeks. RESULTS: The Basso, Beattie and Bresnahan test showed improvement in the animals with the combined therapy compared with the untreated animals, the animals treated with GABAergic cells only and the animals that received BMSCs. The immunohistochemistry analysis of the tissue sections prepared from the animals receiving the combined therapy showed that the transplanted cells were engrafted and integrated into the injured spinal cord; in addition, a significant reduction was seen in the cavitation. CONCLUSIONS: The study shows that the combination of GABAergic cells with BMSCs can improve SCI.


Assuntos
Células-Tronco Mesenquimais/fisiologia , Traumatismos da Medula Espinal/terapia , Ácido gama-Aminobutírico/farmacologia , Animais , Transplante de Medula Óssea/métodos , Feminino , Regeneração Nervosa/fisiologia , Neurotransmissores/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia
8.
Tissue Eng Regen Med ; 16(3): 253-263, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31205854

RESUMO

Background: Retinal degeneration causes blindness, and cell replacement is a potential therapy. The purpose of this study is to formation of pigmented neurospheres in a simple medium, low-cost, high-performance manner over a short period of time while expressing markers of RPE cells and the activation of specific genes of the pigment cells. Also, these neurospheres have the ability to produce a monolayer of retinal pigment epithelium-like cells (RPELC) with the ability of photoreceptor outer segment phagocytosis. Methods: BMSC were isolated from pigmented hooded male rats and were immunoreactive to BMSC markers, then converted into neurospheres, differentiated into pigmented spheres (PS), and characterized using Retinal pigment epithelium-specific 65 kDa protein (RPE65), Retinaldehyde-binding protein 1 (CRALBP) and orthodenticle homeobox 2 (OTX2) markers by immunocytochemistry, RT-PCR and RT-qPCR. The PS were harvested into RPELC. The functionality of RPELC was evaluated by phagocytosis of fluorescein-labeled photoreceptor outer segment. Results: The BMSC immunophenotype was confirmed by immunostained for fibronectin, CD90, CD166 and CD44. These cells differentiated into osteogenic and lipogenic cells. The generated neurospheres were immunoreactive to nestin and stemness genes. The PS after 7-14 days were positive for RPE65 (92.76-100%), CRALBP (95.21-100%) and OTX2 (94.88-100%), and after 30 days RT-PCR, qPCR revealed increasing in gene expression. The PS formed a single layer of RPELC after cultivation and phagocyte photoreceptor outer segments. Conclusion: Bone marrow stromal stem cells can differentiate into functional retinal pigmented epithelium cells in a simple, low-cost, high-performance manner over a short period of time. These cells due to expressing the RPELC genes and markers can be used in cell replacement therapy for degenerative diseases including age-related macular degeneration as well as retinitis pigmentosa.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Transdiferenciação Celular , Irã (Geográfico) , Masculino , Células-Tronco Mesenquimais/citologia , Nestina , Osteogênese , Fatores de Transcrição Otx/genética , Fatores de Transcrição Otx/metabolismo , Fagocitose , Ratos , Degeneração Retiniana/metabolismo , Epitélio Pigmentado da Retina/citologia , cis-trans-Isomerases/genética , cis-trans-Isomerases/metabolismo
9.
Iran J Basic Med Sci ; 21(7): 688-694, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30140407

RESUMO

OBJECTIVES: Human superoxide dismutase 1 (SOD1) is the cytosolic form of this enzyme it detoxifies superoxide anions and attenuates their toxicities and concomitant detrimental effects on the cells. It is believed that the amount of these enzymes present in the oxidative stress-induced diseases is crucial for preventing disease progression. Transfection of rat bone marrow stromal cells (BMSCs) by a constructed vector carrying the human wild-type SOD1 gene, a non-viral gene transfer method, was the main aim of this study. MATERIALS AND METHODS: For this purpose, the rat BMSCs were transfected with the vector using Turbofect reagent and then stabilized. Western-blot and real-time PCR were also used for evaluation of SOD1 expression. RESULTS: Data analysis from RT-PCR and Western-blot techniques revealed that the stable transfected cells could secrete human wild-type SOD1 in the supernatant. Also, the total activity of SOD1 was about 0.5±0.09 U/ml and 0.005±0.002 U/ml in the supernatants of the transfected and not-transfected of rat BMSCs, respectively. CONCLUSION: This study showed that expansion of the stable transfected rat BMSCs by a constructed vector carrying the human wild-type SOD1 gene is capable of secreting the active SOD1 enzyme under ex-vivo conditions. The recommendation of this study is that the same experiment would be applicable for expression of the other form of this enzyme, SOD3, as well. More valuable information could probably be provided about the variety of the diseases caused by superoxide anions toxicities by intervention and application of the non-viral method for expressions of SOD1 and SOD3 enzymes.

10.
Rejuvenation Res ; 21(1): 29-36, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28622077

RESUMO

The proliferation and differentiation potential of adipose-derived stem cells (ADSCs) decline with aging. Moreover, Alzheimer's disease is associated with progressive decline in cholinergic neurons. The purpose of this study is to enhance the proliferation potential of aged rat ADSCs and their differentiation into cholinergic neurons. The ADSCs were collected from aged male rats cultured and treated with different concentrations of sodium selenite for 3 days or glutathione mono ethyl ester (GSH-MEE) for 1 day. Incubating the ADSCs with 27 nM sodium selenite for 3 days significantly increased the relative cell proliferation, compared with the control, without any change in the telomerase activity, the related telomerase gene expression, and the telomere length, but it does improve differentiation of the aged ADSCs to cholinergic neuron-like cells. GSH-MEE at a concentration of 2 mM for 1 day resulted in increased relative cell proliferation, but it did not change the telomerase activity, the related telomerase gene expression, the telomere length, and differentiation potential. Sodium selenite is more effective than GSH-MEE in improving the aged ADSCs' properties. However, both did not have any effect on telomerase activity.


Assuntos
Tecido Adiposo/citologia , Senescência Celular/efeitos dos fármacos , Glutationa/farmacologia , Selenito de Sódio/farmacologia , Células-Tronco/citologia , Telomerase/metabolismo , Animais , Biomarcadores/metabolismo , Separação Celular , Neurônios Colinérgicos/citologia , Neurônios Colinérgicos/efeitos dos fármacos , Neurônios Colinérgicos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Ratos Sprague-Dawley , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Telomerase/genética , Homeostase do Telômero/efeitos dos fármacos
11.
Iran Biomed J ; 22(4): 246-57, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29031245

RESUMO

Background: Oligodendrocyte cell death is among the important features of spinal cord injury, which appears within 15 min and occurs intensely for 4 h after injury, in the rat spinal contusion model. Accordingly, the number of oligodendrocytes progressively reduced within 24 h after injury. Administration of oligodendrocyte-like cells (OLCs) into the lesion area is one of the approaches to counterbalance this condition. Methods: Bone marrow stromal cells were transdifferentiated into neurospheres and then into neural stem cells and later were differentiated into OLCs using triiodothyronine and transplanted into the spinal cord contusion rats. The post-injury functional recovery was explored and compared with the control group using Basso-Beattie-Bresnahan and narrow beam behavioral tests. At the end of 12th week, spinal cord segments T12-L1 were histomorphologically studied by immunohistochemistry. Results: Motor improvement was more obvious during 2nd to 4th weeks and got less prominent during 4th to 12th weeks. Histomorphometric findings indicated that cavity formation decreased in epicenter of transplantation area in experimental groups in comparison with the control groups. Conclusion: The findings obtained in the present study showed that OLC therapy is a potential approach in the treatment of spinal cord traumatic injuries.

12.
Exp Clin Transplant ; 16(2): 204-211, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29025379

RESUMO

OBJECTIVES: Transplantation of stem cells is one of the approaches to treat retinal diseases. Our objective was to determine whether adipose-derived stem cell transplant can survive and migrate in the injured retina using a sodium iodate model for the pigmented retinal epithelium injury. MATERIALS AND METHODS: The adipose-derived stem cells were isolated from male albino Sprague-Dawley rats and labeled with DiI so as to track the transplants in the subretinal space. Retinal pigmented epithelium damage was induced by retro-orbital sinus sodium iodate injection (40 mg/kg) into albino Sprague-Dawley rats. Four weeks after transplantation, the eyeballs were fixed in 4% paraformaldehyde and cut with cryostat. The eyeballs were serially sectioned along the vertical meridian. Cryosections were from the full length of the retina and passing through the optic nerve head. The survival and migration of transplanted cells were assessed. RESULTS: Sodium iodate selectively destroyed the retinal pigmented epithelium layer. The transplanted cells incorporated into the retinal pigmented epithelium layer, perhaps differentiating into a retinal pigmented epithelium phenotype. The transplanted cells were located in the subretinal space; after 4 weeks, some were observed in the retinal pigmented epithelium layer. CONCLUSIONS: We found that adipose-derived stem cells survived for 4 weeks after transplantation and migrated into the retinal pigmented epithelium layer.


Assuntos
Tecido Adiposo/transplante , Movimento Celular , Doenças Retinianas/cirurgia , Epitélio Pigmentado da Retina/patologia , Transplante de Células-Tronco/métodos , Tecido Adiposo/citologia , Animais , Diferenciação Celular , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Iodatos , Masculino , Fenótipo , Ratos Sprague-Dawley , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/patologia
13.
Iran J Basic Med Sci ; 20(3): 316-326, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28392905

RESUMO

OBJECTIVES: To investigate the effect of cinnamaldehyde and eugenol on the telomere-dependent senescence of stem cells. In addition, to search the probable targets of mentioned phytochemicals between human telomere interacting proteins (TIPs) using in silico studies. MATERIALS AND METHODS: Human adipose derived stem cells (hASCs) were studied under treatments with 2.5 µM/ml cinnamaldehyde, 0.1 µg/ml eugenol, 0.01% DMSO or any additive. The expression of TERT, AKT1 and DKC1 genes and the telomere length were assessed over 48-hr treatment. In addition, docking study was conducted to show probable ways through which phytochemicals interact with TIPs. RESULTS: Treated and untreated hASCs had undetectable TERT expression, but they had different AKT1 and DKC1 expression levels (CI=0.95; P<0.05). The telomere lengths were reduced in phytochemicals treated with hASCs when compared with the untreated cells (P<0.05). Docking results showed that the TIPs might be the proper targets for cinnamaldehyde and eugenol. Data mining showed there are many targets for cinnamaldehyde and eugenol in the intracellular environment. CONCLUSION: The general effect of cinnamaldehyde and eugenol is their induction of stem cell senescence. Therefore, they could be applicable as chemo-preventive or antineoplastic agents.

14.
J Neurol Sci ; 375: 137-145, 2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28320116

RESUMO

Neurotrophin 3 (NT-3) is an important factor for promoting prenatal neural development, as well as regeneration, axogenesis and plasticity in postnatal life. Therapy with NT-3 was reported to improve the condition of patients suffering from degenerative diseases and traumatic injuries, however, the disadvantage of NT-3 protein delivery is its short half-life, thus our alternative approach is the use of NT-3 gene therapy. In this study, the bone marrow stromal cells (BMSCs) were isolated from adult rats, cultured for 4 passages and transfected with either pEGFP-N1 or a constructed vector containing murine proNT-3 (pSecTag2/HygroB-murine proNT-3) using Lipofectamine 2000 followed by Hygromycin B (200mg/kg). The transfection efficiency of the transiently transfected BMSCs was evaluated using the green fluorescence protein containing vector (pEGFP-N1). A quantitative evaluation of the NT-3 expression of mRNA using real time qRT-PCR shows that there was double fold increase in NT-3 gene expression compared with non-transfected BMSCs, also, the culture supernatant yielded double fold increase in NT-3 using ELISA technique, the data were supported by immunoblotting technique. This suggests that the use of this transfection technique can be useful for gene therapy in different neurological disorders with neurodegenerative or traumatic origins.


Assuntos
Células da Medula Óssea/metabolismo , Neurotrofina 3/genética , Transfecção , Animais , Antígenos CD/metabolismo , Células Cultivadas , Vetores Genéticos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Camundongos , Neurotrofina 3/metabolismo , RNA Mensageiro/metabolismo , Ratos
15.
J Neurosurg Sci ; 61(5): 504-513, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25963955

RESUMO

BACKGROUND: Peripheral nerve injury is a common lesion in clinical practice and transplantation is one of the most common approaches to its treatment. While nerve graft is used for restoring the defected nerve using autologous or allogenic tissues, Schwann cells are considered as an alternative source. In this study, bone marrow stromal cells (BMSCs) were induced to transdifferentiate into Schwann-like cells (SLCs) using progesterone. METHODS: The BMSCs were collected from the long bones of rats and were transdifferentiated in vitro into SLCs by preinduction with ß-mercaptoethanol and retinoic acid, followed by induction with bFGF, PDGF, forskelin and progesterone. The SLCs were then transplanted in a rat model of sciatic nerve injury with 1-cm gaps. A sciatic function index (SFI), histological, immunohistochemical and ultrastructural studies were used in evaluating the improvement in the nerves regeneration. RESULTS: The results show significant differences in the SFI between the control and the treated groups (P<0.05). The transplant was immunoreactive to S100, and the electron microscopy showed myelination in the transplanted cells. CONCLUSIONS: There were functional and structural improvements in the progesterone-induced SLCs, which were not significantly different from the heregulin-treated ones (positive control) but still significantly different from negative controls.


Assuntos
Transdiferenciação Celular/efeitos dos fármacos , Traumatismos dos Nervos Periféricos , Progesterona/farmacologia , Células de Schwann/transplante , Animais , Axotomia , Modelos Animais de Doenças , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Células de Schwann/efeitos dos fármacos , Nervo Isquiático
16.
Mol Neurobiol ; 54(3): 1978-1991, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-26910814

RESUMO

Creatine was reported to induce bone marrow stromal cells (BMSC) into GABAergic neuron-like cells (GNLC). In a previous study, creatine was used as a single inducer for BMSC into GNLC with low yield. In this study, BMSC-derived neurospheres (NS) have been used in generating GABAergic phenotype. The BMSC were isolated from adult rats and used in generating neurospheres and used for producing neural stem cells (NSC). A combination of all-trans-retinoic acid (RA), the ciliary neurotrophic factor (CNTF), and creatine was used in order to improve the yield of GNLC. We also used other protocols for the transdifferentiation including RA alone; RA and creatine; RA and CNTF; and RA, CNTF, and creatine. The BMSC, NSC, and GNLC were characterized by specific markers. The activity of the GNLC was evaluated using FM1-43. The isolated BMSC expressed Oct4, fibronectin, and CD44. The NS were immunoreactive to nestin and SOX2, the NSC were immunoreactive to nestin, NF68 and NF160, while the GNLC were immunoreactive to GAD1/2, VGAT, GABA, and synaptophysin. Oct4 and c-MYC, pluripotency genes, were expressed in the BMSC, while SOX2 and c-MYC were expressed in the NSC. The activity of GNLC indicates that the synaptic vesicles were released upon stimulation. The conclusion is that the combination of RA, CNTF, and creatine induced differentiation of neurosphere-derived NSC into GNLC within 1 week. This protocol gives higher yield than the other protocols used in this study. The mechanism of induction was clearly associated with several differential pluripotent genes.


Assuntos
Transdiferenciação Celular/fisiologia , Creatina/farmacologia , Neurônios GABAérgicos/fisiologia , Células-Tronco Mesenquimais/fisiologia , Células-Tronco Neurais/fisiologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Transdiferenciação Celular/efeitos dos fármacos , Células Cultivadas , Neurônios GABAérgicos/efeitos dos fármacos , Expressão Gênica , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
17.
J Neurosurg Sci ; 61(5): 486-494, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25283064

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The combination of the transdifferentiated BMSCs into OLCs with the undifferentiated BMSCs improved the contused spinal cord.


Assuntos
Transdiferenciação Celular , Transplante de Células-Tronco Mesenquimais/métodos , Oligodendroglia/transplante , Traumatismos da Medula Espinal , Animais , Feminino , Células-Tronco Mesenquimais/citologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica
18.
Iran J Child Neurol ; 11(4): 23-31, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29201120

RESUMO

OBJECTIVE: Long Term Video-EEG Monitoring (LTM) may give us important information in the preoperative assessment of these patients. We performed this study for the first time in pediatric age group in Iran. MATERIALS AND METHODS: In this cross-sectional study, 43 children between 4 to 18 yr, with intractable epilepsy referred to Shefa Neuroscience Research Center, Tehran, Iranfrom2007-2012, were enrolled to study in order to evaluate their long-term video EEG findings. RESULTS: The patients mean age was10.07 yr, from which 24(65.9%) were boys.Seven patients with definite epileptogenic zone were advised to perform lesionectomy surgery.In two patients, there was not any seizure onset focus but corpus callosotomy was advised to control their frequent falling.Eight cases were recommended to perform electrocorticography or invasive EEG monitoring and26 cases to adjust medical treatment. In three cases, there was not any electrical seizure activity during clinical attacks, so discontinuing anti-epileptic drugs were recommended fordiagnosis of conditions that mimic epilepsy. CONCLUSION: It is necessary to perform LTM in patients with refractory epilepsy in order to determine their treatment strategy. If there is any doubt about pseudoseizureLTM can help to differentiate epilepsy from conditions that mimic epilepsy.

19.
J Spinal Cord Med ; 39(3): 265-71, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26182184

RESUMO

CONTEXT: Use of a handrim wheelchair could force the wrist into extreme excursions and encroachment of the median nerve. OBJECTIVE: We performed a study of the prevalence of carpal tunnel syndrome in prolonged wheelchair users. DESIGN AND SETTING: A cross-sectional study was conducted for one year in an outpatient clinic of spinal cord injury. PARTICIPANTS: Patients had traumatic injury at the first thoracic level and below, with time since injury of at least 5 years. OUTCOME MEASURE: The prevalence of carpal tunnel syndrome by history taking, clinical examinations and motor and sensory nerve conduction studies of median nerve performed for both hands. RESULTS: Participants (N = 297) were all male. Mean (SD) age and duration since injury were 48 (8.5) and 23 (6.6) years, respectively. A significant difference in median duration of injury based on the severity of the syndrome (P < 0.001), and a significant trend in time since injury for the severity (P (one tailed) < 0.001) were seen. There was a significant difference in the median age among the groups (P = 0.009), and the median increased with the severity (P (one tailed) = 0.001). CONCLUSIONS: Carpal tunnel syndrome is a common side effect of the long time use of wheelchair, and its severity is associated with duration of wheelchair use and age. Alternative methods for wheelchair propulsion should be developed to diminish the likelihood of the syndrome.


Assuntos
Síndrome do Túnel Carpal/epidemiologia , Traumatismos da Medula Espinal/epidemiologia , Cadeiras de Rodas/efeitos adversos , Adulto , Idoso , Síndrome do Túnel Carpal/etiologia , Humanos , Masculino , Nervo Mediano/patologia , Pessoa de Meia-Idade , Prevalência , Distribuição Aleatória
20.
In Vitro Cell Dev Biol Anim ; 52(7): 772-81, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27251157

RESUMO

The proliferation and differentiation potential of aged bone marrow stromal cells (BMSCs) are significantly reduced. In order to improve the performance of the aged BMSCs, these cells were treated with 2 mM glutathione monoethyl ester (GSH-MEE) for 24 h. Proliferation rate, telomerase activity, telomere length, and differentiation to cholinergic neuron-like cells (CNLCs) were observed to increase. Though, the expression level of telomerase reverse transcriptase gene increased, but CTC1 and TEN1 genes from Ctc1-Stn1-Ten1 complex encoding proteins with regulatory function significantly decreased. Trypan blue exclusion assay was used to analyze the proliferation and, while telomere length, its several related gene expressions, and telomerase activity were measured using the real time reverse transcription-polymerase chain reaction and polymerase chain reaction enzyme-linked immunosorbent assay techniques, respectively. CNLCs differentiation potential was evaluated by estimating the percentage of choline acetyltransferase immunereactive cells.The results suggested that GSH-MEE could improve aged rat BMSC properties and would be of potential benefit for enhancing the performance of aged people's BMSCs.


Assuntos
Glutationa/análogos & derivados , Telomerase/biossíntese , Proteínas de Ligação a Telômeros/biossíntese , Telômero/genética , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colina O-Acetiltransferase/biossíntese , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Glutationa/administração & dosagem , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Ratos , Telomerase/genética , Telômero/metabolismo , Proteínas de Ligação a Telômeros/genética
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