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1.
Transl Neurosci ; 15(1): 20220343, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38979518

ABSTRACT

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.

2.
Tissue Eng Regen Med ; 16(3): 253-263, 2019 06.
Article in English | MEDLINE | ID: mdl-31205854

ABSTRACT

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.


Subject(s)
Cell Differentiation/physiology , Mesenchymal Stem Cells/metabolism , Retinal Pigment Epithelium/metabolism , Animals , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Transdifferentiation , Iran , Male , Mesenchymal Stem Cells/cytology , Nestin , Osteogenesis , Otx Transcription Factors/genetics , Otx Transcription Factors/metabolism , Phagocytosis , Rats , Retinal Degeneration/metabolism , Retinal Pigment Epithelium/cytology , cis-trans-Isomerases/genetics , cis-trans-Isomerases/metabolism
3.
Iran J Basic Med Sci ; 21(7): 688-694, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30140407

ABSTRACT

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.

4.
Spinal Cord ; 56(5): 487-493, 2018 05.
Article in English | MEDLINE | ID: mdl-29277840

ABSTRACT

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.


Subject(s)
Absorptiometry, Photon , Bone Density , Spinal Cord Injuries/diagnostic imaging , Spine/diagnostic imaging , Tomography, X-Ray Computed , Chronic Disease , Humans , Male , Middle Aged , Observer Variation , Osteoporosis/complications , Osteoporosis/diagnostic imaging , Psychometrics , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Spinal Cord Injuries/complications
5.
Iran Biomed J ; 22(4): 246-57, 2018 07.
Article in English | MEDLINE | ID: mdl-29031245

ABSTRACT

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.

6.
Rejuvenation Res ; 21(1): 29-36, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28622077

ABSTRACT

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.


Subject(s)
Adipose Tissue/cytology , Cellular Senescence/drug effects , Glutathione/pharmacology , Sodium Selenite/pharmacology , Stem Cells/cytology , Telomerase/metabolism , Animals , Biomarkers/metabolism , Cell Separation , Cholinergic Neurons/cytology , Cholinergic Neurons/drug effects , Cholinergic Neurons/metabolism , Gene Expression Regulation/drug effects , Male , Neural Stem Cells/cytology , Neural Stem Cells/drug effects , Neural Stem Cells/metabolism , Rats, Sprague-Dawley , Stem Cells/drug effects , Stem Cells/metabolism , Telomerase/genetics , Telomere Homeostasis/drug effects
7.
Exp Clin Transplant ; 16(2): 204-211, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29025379

ABSTRACT

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.


Subject(s)
Adipose Tissue/transplantation , Cell Movement , Retinal Diseases/surgery , Retinal Pigment Epithelium/pathology , Stem Cell Transplantation/methods , Adipose Tissue/cytology , Animals , Cell Differentiation , Cell Survival , Cells, Cultured , Disease Models, Animal , Iodates , Male , Phenotype , Rats, Sprague-Dawley , Retinal Diseases/chemically induced , Retinal Diseases/pathology
8.
Iran J Child Neurol ; 11(4): 23-31, 2017.
Article in English | MEDLINE | ID: mdl-29201120

ABSTRACT

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.

9.
Iran J Basic Med Sci ; 20(3): 316-326, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28392905

ABSTRACT

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.

10.
J Neurol Sci ; 375: 137-145, 2017 Apr 15.
Article in English | MEDLINE | ID: mdl-28320116

ABSTRACT

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.


Subject(s)
Bone Marrow Cells/metabolism , Neurotrophin 3/genetics , Transfection , Animals , Antigens, CD/metabolism , Cells, Cultured , Genetic Vectors , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Mice , Neurotrophin 3/metabolism , RNA, Messenger/metabolism , Rats
11.
J Neurosurg Sci ; 61(5): 504-513, 2017 Oct.
Article in English | MEDLINE | ID: mdl-25963955

ABSTRACT

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.


Subject(s)
Cell Transdifferentiation/drug effects , Peripheral Nerve Injuries , Progesterone/pharmacology , Schwann Cells/transplantation , Animals , Axotomy , Disease Models, Animal , Male , Mesenchymal Stem Cells/drug effects , Rats , Rats, Sprague-Dawley , Schwann Cells/drug effects , Sciatic Nerve
12.
J Neurosurg Sci ; 61(5): 486-494, 2017 Oct.
Article in English | MEDLINE | ID: mdl-25283064

ABSTRACT

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.


Subject(s)
Cell Transdifferentiation , Mesenchymal Stem Cell Transplantation/methods , Oligodendroglia/transplantation , Spinal Cord Injuries , Animals , Female , Mesenchymal Stem Cells/cytology , Rats , Rats, Sprague-Dawley , Recovery of Function
13.
Cell Mol Neurobiol ; 37(2): 275-289, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27107758

ABSTRACT

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.


Subject(s)
Adipocytes/physiology , Cell Transdifferentiation/physiology , Gene Expression Regulation , Motor Neurons/physiology , Neural Stem Cells/physiology , Adipose Tissue/cytology , Adipose Tissue/physiology , Animals , Cells, Cultured , Coculture Techniques , Female , Motor Neurons/cytology , Rats , Rats, Sprague-Dawley
14.
Mol Neurobiol ; 54(3): 1978-1991, 2017 04.
Article in English | MEDLINE | ID: mdl-26910814

ABSTRACT

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.


Subject(s)
Cell Transdifferentiation/physiology , Creatine/pharmacology , GABAergic Neurons/physiology , Mesenchymal Stem Cells/physiology , Neural Stem Cells/physiology , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/physiology , Cell Transdifferentiation/drug effects , Cells, Cultured , GABAergic Neurons/drug effects , Gene Expression , Mesenchymal Stem Cells/drug effects , Neural Stem Cells/drug effects , Rats , Rats, Sprague-Dawley
15.
In Vitro Cell Dev Biol Anim ; 52(7): 772-81, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27251157

ABSTRACT

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.


Subject(s)
Glutathione/analogs & derivatives , Telomerase/biosynthesis , Telomere-Binding Proteins/biosynthesis , Telomere/genetics , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Choline O-Acetyltransferase/biosynthesis , Gene Expression Regulation, Developmental/drug effects , Glutathione/administration & dosage , Humans , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Neurons/cytology , Neurons/metabolism , Rats , Telomerase/genetics , Telomere/metabolism , Telomere-Binding Proteins/genetics
16.
J Ophthalmic Vis Res ; 11(1): 70-7, 2016.
Article in English | MEDLINE | ID: mdl-27195089

ABSTRACT

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.

17.
J Neurol Sci ; 362: 174-81, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26944143

ABSTRACT

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.


Subject(s)
Amyotrophic Lateral Sclerosis/therapy , Bone Marrow Cells/physiology , Cell- and Tissue-Based Therapy/methods , Adult , Aged , Electromyography , Evoked Potentials, Motor/physiology , Feasibility Studies , Female , Humans , Injections, Spinal , Male , Middle Aged , Muscle Strength
18.
Avicenna J Phytomed ; 6(6): 643-657, 2016.
Article in English | MEDLINE | ID: mdl-28078245

ABSTRACT

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 in vitro 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.

19.
Am J Mens Health ; 10(1): 24-31, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25432464

ABSTRACT

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.


Subject(s)
Erectile Dysfunction/etiology , Quality of Life , Sexual Behavior/psychology , Spinal Cord Injuries/complications , Veterans/statistics & numerical data , Cross-Sectional Studies , Erectile Dysfunction/psychology , Humans , Iran , Male , Middle Aged , Sexual Behavior/statistics & numerical data , Spinal Cord Injuries/psychology , Surveys and Questionnaires , Veterans/psychology , Veterans Health
20.
J Tissue Eng Regen Med ; 10(3): 199-208, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25312025

ABSTRACT

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, ß-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.


Subject(s)
Cell Differentiation/drug effects , Hydrogels/pharmacology , Neural Stem Cells/cytology , Oligopeptides/pharmacology , Polyethylene Glycols/pharmacology , Tenascin/pharmacology , Animals , Bone Marrow Cells/cytology , Cell Aggregation/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Neural Stem Cells/drug effects , Phenotype , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Stromal Cells/cytology , Stromal Cells/drug effects
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