Publications by authors named "Taher Taheri"

33 Publications

Generation of Retinal Pigmented Epithelium-Like Cells from Pigmented Spheres Differentiated from Bone Marrow Stromal Cell-Derived Neurospheres.

Tissue Eng Regen Med 2019 06 3;16(3):253-263. Epub 2019 May 3.

Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Rashid Yasemi Street, Upper than Mirdamad St. Vali- Asr. St., 1996816747 Tehran, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13770-019-00183-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542896PMC
June 2019

Human wild-type superoxide dismutase 1 gene delivery to rat bone marrow stromal cells: its importance and potential future trends.

Iran J Basic Med Sci 2018 Jul;21(7):688-694

Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Tehran, Iran.

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 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 gene is capable of secreting the active SOD1 enzyme under 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22038/IJBMS.2018.27721.6879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098954PMC
July 2018

Investigating comparability of quantitative computed tomography with dual energy x-ray absorptiometry in assessing bone mineral density of patients with chronic spinal cord injury.

Spinal Cord 2018 05 26;56(5):487-493. Epub 2017 Dec 26.

Department of Physical Medicine and Rehabilitation, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41393-017-0041-3DOI Listing
May 2018

Long-term Video-EEG Monitoring Findings in Children and Adolescents with Intractable Epilepsy.

Iran J Child Neurol 2017 ;11(4):23-31

Shefa neuroscience research Center, Rashid Yasemi ST,Tehran, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703625PMC
January 2017

Decrease in Cavity Size and Oligodendrocyte Cell Death Using Neurosphere-Derived Oligodendrocyte-Like Cells in Spinal Cord Contusion Model

Iran Biomed J 2018 07 15;22(4):246-57. Epub 2017 Oct 15.

Department of Clinical Biochemistry, Faculty of Paramedicine, Ilam University of Medical Sciences, Ilam, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949127PMC
http://dx.doi.org/10.22034/ibj.22.4.246DOI Listing
July 2018

Survival and Migration of Adipose-Derived Stem Cells Transplanted in the Injured Retina.

Exp Clin Transplant 2018 Apr 12;16(2):204-211. Epub 2017 Oct 12.

From the Department of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6002/ect.2016.0235DOI Listing
April 2018

A Comparative Study of the Effects of Sodium Selenite and Glutathione Mono Ethyl Ester on Aged Adipose-Derived Stem Cells: The Telomerase and Cellular Responses.

Rejuvenation Res 2018 Feb 22;21(1):29-36. Epub 2017 Aug 22.

3 Shefa Neuroscience Research Center , Khatam Alanbia Hospital, Tehran, Iran .

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/rej.2017.1961DOI Listing
February 2018

Cinnamaldehyde and eugenol change the expression folds of AKT1 and DKC1 genes and decrease the telomere length of human adipose-derived stem cells (hASCs): An experimental and in silico study.

Iran J Basic Med Sci 2017 Mar;20(3):316-326

Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.

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 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; <0.05). The telomere lengths were reduced in phytochemicals treated with hASCs when compared with the untreated cells (<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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22038/IJBMS.2017.8362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378970PMC
March 2017

In vitro non-viral murine pro-neurotrophin 3 gene transfer into rat bone marrow stromal cells.

J Neurol Sci 2017 Apr 21;375:137-145. Epub 2017 Jan 21.

Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2017.01.058DOI Listing
April 2017

The effects of cinnamaldehyde and eugenol on human adipose-derived mesenchymal stem cells viability, growth and differentiation: a cheminformatics and study.

Avicenna J Phytomed 2016 Nov-Dec;6(6):643-657

Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.

Objective: The aim of this study was to estimate the cheminformatics and qualitative structure-activity relationship (QSAR) of cinnamaldehyde and eugenol. The effects of cinnamaldehyde and eugenol on the viability, doubling time and adipogenic or osteogenic differentiations of human adipose-derived mesenchymal stem cells (hASCs) were also investigated.

Materials And Methods: QSAR and toxicity indices of cinnamaldehyde and eugenol were evaluated using cheminformatics tools including Toxtree and Toxicity Estimation Software Tool (T.E.S.T) and molinspiration server. Besides, their effects on the hASCs viability, doubling time and differentiation to adipogenic or osteogenic lineages were evaluated.

Results: Cinnamaldehyde is predicted to be more lipophilic and less toxic than eugenol. Both phytochemicals may be developmental toxicants. They probably undergo hydroxylation and epoxidation reactions by cytochrome-P450. The 2.5 µM/ml cinnamaldehyde and 0.1 µg/ml eugenol did not influence hASCs viability following 72 hr of treatment. But higher concentrations of these phytochemicals insignificantly increased hASCs doubling time till 96 hr, except 1 µg/ml eugenol for which the increase was significant. Only low concentrations of both phytochemicals were tested for their effects on the hASCs differentiation. The 2.5 µM/ml cinnamaldehyde and 0.1 µg/ml eugenol enhanced the osteogenesis and decreased the adipogenesis of hASCs meaningfully.

Conclusion: According to the cheminformatics analysis and study, cinnamaldehyde and eugenol are biocompatible and low toxic for hASCs. Both phytochemicals may be suitable for regenerative medicine and tissue engineering when used at low concentrations, but maybe useful for neoplastic growth inhibition when used at high concentrations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216609PMC
January 2017

Stimulation of cell proliferation by glutathione monoethyl ester in aged bone marrow stromal cells is associated with the assistance of TERT gene expression and telomerase activity.

In Vitro Cell Dev Biol Anim 2016 Aug 1;52(7):772-81. Epub 2016 Jun 1.

Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11626-016-0021-5DOI Listing
August 2016

Histological and Electrophysiological Changes in the Retinal Pigment Epithelium after Injection of Sodium Iodate in the Orbital Venus Plexus of Pigmented Rats.

J Ophthalmic Vis Res 2016 Jan-Mar;11(1):70-7

Shefa Neuroscience Research Center, Khatam-Al-Anbia Hospital, Tehran, Iran.

Purpose: To characterize histopathologic and electroretinographic (ERG) changes in the retina of pigmented rats injected with sodium iodate in order to establish a model of retinal degeneration for future cell therapy studies.

Methods: In 50 male pigmented rats weighing 250-300 grams, NaIO3 was injected into the left orbital venous plexus at 40 and 60 mg/kg doses (25 eyes in each group). Fourteen rats received phosphate buffered saline (PBS) injection in their left orbital plexus and were considered as the sham-control group. Histopathologic and ERG studies were performed at baseline and on days 1, 7, 14 and 28 after the injections.

Results: Progressive retinal pigment epithelial (RPE) changes were observed from the first day of injection in both the 40 and 60 mg/kg study groups in a dose dependent manner. These changes manifested as loss of melanin pigment and accumulation of lipofuscin in RPE cells with subsequent cell death and patchy loss of RPE cells (in flat mounts), as well as thinning of the outer nuclear layer and later the inner nuclear layer in the succeeding days. ERG showed a progressive and significant decrease in a- and b- wave amplitudes in both case groups relative to baseline values and the controls (P < 0.05).

Conclusion: NaIO3 injection into the retrobulbar venous plexus of pigmented rats can result in significant and progressive damage to the RPE and subsequently to the neuroretina of the injected eye, and may serve as a model of retinal degeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/2008-322X.180695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860991PMC
May 2016

Motor Neuron Transdifferentiation of Neural Stem Cell from Adipose-Derived Stem Cell Characterized by Differential Gene Expression.

Cell Mol Neurobiol 2017 Mar 23;37(2):275-289. Epub 2016 Apr 23.

Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10571-016-0368-xDOI Listing
March 2017

Intraspinal delivery of bone marrow stromal cell-derived neural stem cells in patients with amyotrophic lateral sclerosis: A safety and feasibility study.

J Neurol Sci 2016 Mar 26;362:174-81. Epub 2016 Jan 26.

Department of Spinal Cord Injury, Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Tehran, Iran.

Background: Stem cells have been used in several studies with different methodologies to treat patients with ALS.

Methods: In this safety and feasibility study, 11 patients with definite or probable ALS according to El Escorial criteria were selected. 3 patients were excluded due to inadequate bone marrow or safety measures after acquisition of bone marrow. Bone marrow stromal cell-derived neural stem cells were injected in C7-T1 spinal cord under general anesthesia. Patients were followed for 12months after injection with manual muscle testing, ALSFRS-R, quality of life changes, pulmonary function test and electromyography.

Results: None of the patients had perioperative mortality or major morbidity. One patient had temporary deterioration in lower extremities after injection which improved after a few weeks. In the 12months post-injection, only one patient died due to pulmonary embolism. From the remaining 7 patients, all had a stable course after 4months and 5 were stable for the first 8months post-injection and deteriorated afterwards.

Discussion: In this study, intraspinal injection of bone marrow derived neural stem cells appears to be safe. Patients experienced a temporary stabilization for the first few months post-injection and then gradually deteriorated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2016.01.051DOI Listing
March 2016

Creatine Enhances Transdifferentiation of Bone Marrow Stromal Cell-Derived Neural Stem Cell Into GABAergic Neuron-Like Cells Characterized With Differential Gene Expression.

Mol Neurobiol 2017 04 24;54(3):1978-1991. Epub 2016 Feb 24.

Middle Euphrates Neuroscience Center-Kufa College of Medicine, Annajaf, Iraq.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-016-9782-9DOI Listing
April 2017

The prevalence of carpal tunnel syndrome among long-term manual wheelchair users with spinal cord injury: A cross-sectional study.

J Spinal Cord Med 2016 05 16;39(3):265-71. Epub 2015 Jul 16.

a Department of Physical Medicine and Rehabilitation, School of Medicine , Baqiatallah University of Medical Sciences , Tehran , Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1179/2045772315Y.0000000033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073759PMC
May 2016

Comparison of health related quality of life between two groups of veteran and non-veteran spinal cord injured patients.

Med J Islam Repub Iran 2015 15;29:198. Epub 2015 Apr 15.

Professor, Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476210PMC
July 2015

Progesterone-induced transdifferentiation of bone marrow stromal cells into Schwann cells improves sciatic nerve transection outcome in a rat model.

J Neurosurg Sci 2017 Oct 12;61(5):504-513. Epub 2015 May 12.

Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran.

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 β-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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0390-5616.16.02861-7DOI Listing
October 2017

Human ciliary neurotrophic factor-overexpressing stable bone marrow stromal cells in the treatment of a rat model of traumatic spinal cord injury.

Cytotherapy 2015 Jul 1;17(7):912-21. Epub 2015 May 1.

Shefa Neuroscience Research Center, Khatam Al-Anbia Hospital, Tehran, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcyt.2015.03.689DOI Listing
July 2015

Evaluation of pain and its effect on quality of life and functioning in men with spinal cord injury.

Korean J Pain 2015 Apr 1;28(2):129-36. Epub 2015 Apr 1.

Sina Trauma and Surgery Research Center (STSRC), Tehran University Medical Sciences, Tehran, Iran. ; Department of Neurosurgery, Tehran University of Medical Sciences, Tehran, Iran.

Background: Pain is one of the most important consequences of spinal cord injury (SCI). It may affect several aspects of life, especially the quality of life (QoL). Hence, this study was conducted to establish an understanding of pain and its correlates and effects on patients with SCI in our community.

Methods: In a cross-sectional study, 58 male veterans suffering from SCI were admitted to our center for a regular follow-up. Demographic and SCI-related descriptive information were gathered using a self-reported questionnaire. To evaluate the patients' pain quality and the effect of pain on daily life, a questionnaire in 3 parts of lumbar, cervical and shoulder pain was administered. EuroQoL questionnaire and General Health Questionnaire (GHQ) 12 were also used to assess the patients' QoL.

Results: The mean age of the participants was 45.91 ± 6.69 with mean injury time of 25.54 ± 5.91. forty-four patients (75.9%) reported pain, including lumbar pain (63%), cervical pain (39%) and shoulder pain (51%). The presence of pain was associated with lower QoL. Patients with lumbar pain reported a significant amount of pain affecting their daily life and this effect was higher in patients with lower GHQ score or anxiety/depressive disorder.

Conclusions: Musculoskeletal pain, is a common complaint in veterans with SCI and is inversely associated with functioning and general health status. Lumbar and shoulder pain affects patient's daily living more than cervical pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3344/kjp.2015.28.2.129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387458PMC
April 2015

Evaluation of Sexual Function and Its Contributing Factors in Men With Spinal Cord Injury Using a Self-Administered Questionnaire.

Am J Mens Health 2016 Jan 27;10(1):24-31. Epub 2014 Nov 27.

Tehran University of Medical Sciences, Tehran, Iran

Sexual activity is an important aspect of life in patients with spinal cord injury (SCI), rated as one of the top priorities for recovery of function. This study was conducted to establish an understanding of the severity of erectile dysfunction (ED), a major component of male sexual activity, and its correlates in patients with SCI in our community. In a cross-sectional study, 37 male veterans with SCI admitted for regular follow-up at our center were recruited. Demographic and SCI-related descriptive information was gathered through a self-administered questionnaire. Sexual Health Inventory for Men was used to assess the presence and severity of ED. Euro Quality of Life questionnaire and General Health Questionnaire (GHQ-12) were also administered. The mean age of the participants was 45.7 ± 6.5 years with injury duration of 24.7 ± 6.2 years. Mean GHQ-12 score of 3.65 ± 3.38 and mean Sexual Health Inventory for Men score of 11.57 ± 5.28 were measured. All participants had ED, and 27% were suffering from severe ED. Sleep deprivation, worse GHQ-12 score, and hypertension were significantly associated with higher risk of much severe ED (p < .05). In conclusion, ED is a common problem in veterans with SCI and is inversely associated with their general health status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1557988314555122DOI Listing
January 2016

Survival, proliferation and differentiation enhancement of neural stem cells cultured in three-dimensional polyethylene glycol-RGD hydrogel with tenascin.

J Tissue Eng Regen Med 2016 Mar 13;10(3):199-208. Epub 2014 Oct 13.

Shefa Neuroscience Research Centre, Khatam Al-Anbia Hospital, Tehran, Iran.

Polyethylene glycol hydrogel (PEG) conjugated with arginyl glycyl aspartic acid (RGD) (PEG-RGD) has been considered to be a scaffold in three-dimensional (3D) culture that improves neurite outgrowth; on the other hand, tenascin C controls neural growth and differentiation. In this study, the effect of a combined RGD and tenascin C mixture in 3D culture (3D-PEG-RGD-TnC) on the survival, growth and differentiation of neural stem cells. The viability of the culture has been evaluated by live/dead assay and the results show that the viability of NSCs in 3D-PEG-RGD-TnC is significantly higher than its value in 3D-PEG-RGD. The proliferation was evaluated by MTS test and was found to be slightly improved but statistically not significant. Accordingly, the differentiation was evaluated by immunoreactivity to nestin, neurofilament 68, neurofilament 160, neurofilament 200 and GFAP; and the expression of nestin, neuro D, musashi1, β-tubulin III, GFAP, MBP and Oct4 was studied using RT-PCR. The results showed enhancement of the differentiation of NSCs into the neuronal phenotype in 3D-PEG-RGD-TnC. The morphology of NSCs cultured in 3D-PEG-RGD-TnC showed neurite outgrowths and increase in the contact between the differentiated cells' extensions. The conclusion of this study was that NSC survival, proliferation and differentiation are enhanced when the cells are cultured in 3D-PEG-RGD-TnC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/term.1958DOI Listing
March 2016

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

J Neurosurg Sci 2017 Oct 6;61(5):486-494. Epub 2014 Oct 6.

Middle Euphrates Neuroscience Center, College of Medicine, Kufa University, Annajaf Al-Ashraf, Iraq.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0390-5616.16.03061-7DOI Listing
October 2017

Intraspinal transplantation of motoneuron-like cell combined with delivery of polymer-based glial cell line-derived neurotrophic factor for repair of spinal cord contusion injury.

Neural Regen Res 2014 May;9(10):1003-13

Shefa Neuroscience Research Center at Khatam Al-Anbia Hospital, Tehran, Iran.

To evaluate the effects of glial cell line-derived neurotrophic factor transplantation combined with adipose-derived stem cells-transdifferentiated motoneuron delivery on spinal cord contusion injury, we developed rat models of spinal cord contusion injury, 7 days later, injected adipose-derived stem cells-transdifferentiated motoneurons into the epicenter, rostral and caudal regions of the impact site and simultaneously transplanted glial cell line-derived neurotrophic factor-gelfoam complex into the myelin sheath. Motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery reduced cavity formations and increased cell density in the transplantation site. The combined therapy exhibited superior promoting effects on recovery of motor function to transplantation of glial cell line-derived neurotrophic factor, adipose-derived stem cells or motoneurons alone. These findings suggest that motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery holds a great promise for repair of spinal cord injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1673-5374.133159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146307PMC
May 2014

Decreased GFAP expression and improved functional recovery in contused spinal cord of rats following valproic acid therapy.

Neurochem Res 2014 Dec 10;39(12):2319-33. Epub 2014 Sep 10.

Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-014-1429-5DOI Listing
December 2014

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

Tissue Cell 2014 Dec 20;46(6):462-9. Epub 2014 Aug 20.

Middle Euphrates Neuroscience Center, Kufa University,College of Medicine, Annajaf Al-Ashraf, Iraq.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tice.2014.08.003DOI Listing
December 2014

Relationship between HLA-DRB1* 11/15 genotype and susceptibility to multiple sclerosis in Iran.

J Neurol Sci 2014 Oct 16;345(1-2):92-6. Epub 2014 Jul 16.

Shefa Neurosciences Research Center, Tehran, Islamic Republic of Iran; Tehran University of Medical Sciences, Department of Medical Genetics, Cancer Institute, Tehran, Islamic Republic of Iran. Electronic address:

Background & Objectives: Analysis of the role of different alleles of human leukocyte antigen (HLA) in multiple sclerosis (MS) patients is necessary in many populations and geographical areas. The aim of the present study was to investigate the frequency of HLA-DRB1 genes and its influence on susceptibility to MS, comparing with that in control group.

Design And Setting: Two groups of case-control of multiple sclerosis patients referred to clinic at Khatam hospitals were studied. The first group consisted of 73 multiple sclerosis patients and the second group comprised 40 healthy volunteers with no known history of MS, living in Tehran.

Patients And Methods: The sample population consisted of 73 consecutive non-selected patients diagnosed with MS according to the McDonald criteria (2010) at the outpatient clinic for multiple sclerosis, 62 (85%) presented with RRMS and 11 (15%) with SPMS. The frequency of HLA-DRB1 alleles was determined in 73 MS patients (with age of 18-56) and 40 healthy subjects in Iran. These consisted of 57 females and 16 males. HLA-DRB1 allele types were identified by polymerase chain reaction products of 24 pair primers for low resolution SSP typing (PCR-SSP).

Results: The HLA-DRB1* 11/15 genotype was detected highest (6 times) in patients compare to normal control population (p-value 0.062), whereas the DRB1 4/11 genotype was detected highest (4 times) in controls compare to MS patients (p-value 0.033). The data showed that HLA-DRB1*03 is significantly more in patients compare to control normal people (p-value 0.0021) as well as DRB1 14 and 16 are significantly more in control normal people, compare to MS patients (p-values 0.0789 and 0.035).

Conclusion: Allele frequency among patients with positive history of multiple sclerosis disease showed that DRB1 11 allele has a significantly low rate in MS patients with positive history compare to other patients. In contrast DRB1 15 allele has a significantly high rate in MS patients with positive history compare to other patients. The frequencies of other alleles were not significantly different between the MS patients and the control group. The frequency of the HLA-DRB1* 11/15 genotype detected in the present study showed that this genotype is partially significant factor for MS susceptibility and development in Iran.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2014.07.013DOI Listing
October 2014

Non-viral human proGDNF gene delivery to rat bone marrow stromal cells under ex vivo conditions.

J Neurol Sci 2014 Apr 31;339(1-2):81-6. Epub 2014 Jan 31.

Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran.

Glial cell line-derived neurotrophic factor (GDNF) is one of the most important proteins playing a pivotal role in growing and repairing of the nervous system. GDNF therapy is one of the suggested options in the treatment of neurodegenerative diseases. Limitations in the viral gene delivery and its side effects after therapy have encouraged us to use a non-viral method one for this purpose. We transfected rat bone marrow stromal cells (BMSCs) in ex vivo conditions using Lipofectamine 2000 reagent with pEGFP-C1 and a constructed vector carrying the human proGDNF (pSecTag2/HygroB-human proGDNF), transiently and stably, respectively. The rate of transient transfection of rat BMSCs was eight percent and transfected rat BMSCs with pSecTag2/HygroB-human proGDNF stabilized by adding Hygromycin B in cell culture medium at 200 μg/ml. Semi-quantitative data analysis from Western-blot technique showed that stable transfected cells secrete GDNF at higher level in comparison with control cells (6.530 fold in the supernatant). The present study supports the utility of liposome-mediated transfection for overexpressing human GDNF in rat BMSCs. For this purpose and in order to get more yield of human GDNF secretion from the stable transfected rat BMSCs, we used a vector containing another signal sequence instead of its own pre-segment of proGDNF protein. This is the first report in this regard and the data presented will be potentially useful for human gene transfer therapies in a variety of neurodegenerative diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2014.01.025DOI Listing
April 2014

Microglial activation in rat experimental spinal cord injury model.

Iran Biomed J 2013 ;17(4):214-20

Dept. of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Background: The present study was designed to evaluate the secondary microglial activation processes after spinal cord injury (SCI).

Methods: A quantitative histological study was performed to determine ED-1 positive cells, glial cell density, and cavitation size in untreated SCI rats at days 1, 2, and 4, and weeks 1, 2, 3, and 4.

Results: The results of glial cell quantification along the 4900-µm long injured spinal cord showed a significant increase in glial cell density percentage at day 2 as compared to other days. Whereas the highest increase in ED-1 immunoreactive cells (monocyte/phagocyte marker in rats) was observed at day 2 (23.15%) post-injury. Evaluation of cavity percentage showed a significant difference between weeks 3 and 4 post-injury groups.

Conclusions: This study provides a new insight into the multiphase immune response to SCI, including cellular inflammation, macrophages/microglia activation, glial cell density, and cavitation. Better understanding of the inflammatory processes associated with acute SCI would permit the development of better therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882925PMC
http://dx.doi.org/10.6091/ibj.1213.2013DOI Listing
July 2014

Improvement of contusive spinal cord injury in rats by co-transplantation of gamma-aminobutyric acid-ergic cells and bone marrow stromal cells.

Cytotherapy 2013 Sep 25;15(9):1073-85. Epub 2013 Jun 25.

Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

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 β-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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcyt.2013.05.002DOI Listing
September 2013