Generation of Human-induced Pluripotent Stem Cells Derived From Dermal Fibroblast of Schizophrenic Patients.

Introduction: Schizophrenia (SCZ) is a psychiatric disorder caused by environmental, social, and genetic factors. This phenomenon is a severe neuropsychiatric disorder with a 1% worldwide prevalence. As SCZ is an exclusively human disorder, animal models cannot mimic SCZ pathophysiology. Thus, it is crucial to develop a novel human-based specific model of SCZ to elucidate mechanisms of the occurrence of the disease. In this regard, the aim of this study was reprogramming somatic cells to human-induced pluripotent stem cells (hiPSCs), with possible potency to transformed to specific neural stem cells. Methods: In the present study, we directly reprogrammed the isolated human ear dermal fibroblasts (HDFs) from schizophrenic patients into hiPSCs using some episomal agents in Matrigel-coated plates. The existence of pluripotency markers was confirmed by the immunocytochemistry (ICC) test and alkaline phosphatase protocol. We performed karyotype analysis to ensure the maintenance of the normal chromosomes. Results: Analysis of colonies exhibited intense alkaline phosphatase engagement and Oct4, SSEA4, Nanog, and Tra-1-60. HiPSCs showed normal karyotypes and were potent to differentiate into ectoderm, endoderm, and mesoderm. Conclusion: This study showed human dermal mesenchymal fibroblasts taken from schizophrenic patients can be reprogrammed to hiPSCs, with potential to transformation to three germ layers with sufficient expression of relate molecular markers. This is the first steps to produce SCZ specific neural stem cells, which can be used in the assessment of cellular changes in schizophrenia and possible effects of antipsychotic agents. .

CHO cell engineering via targeted integration of circular miR-21 decoy using CRISPR/RMCE hybrid system.

Chinese hamster ovary (CHO) cells, widely acknowledged as the preferred host system for industrial recombinant protein manufacturing, play a crucial role in developing pharmaceuticals, including anticancer therapeutics. Nevertheless, mammalian cell-based biopharmaceutical production methods are still beset by cellular constraints such as limited growth and poor productivity. MicroRNA-21 (miR-21) has a major impact on a variety of malignancies, including glioblastoma multiforme (GBM). However, reduced productivity and growth rate have been linked to miR-21 overexpression in CHO cells. The current study aimed to engineer a recombinant CHO (rCHO) cell using the CRISPR-mediated precise integration into target chromosome (CRIS-PITCh) system coupled with the Bxb1 recombinase-mediated cassette exchange (RMCE) to express a circular miR-21 decoy (CM21D) with five bulged binding sites for miR-21 sponging. Implementing the ribonucleoprotein (RNP) delivery method, a landing pad was inserted into the genome utilizing the CRIS-PITCh technique. Subsequently, the CM21D cassette flanked by Bxb1 attB was then retargeted into the integrated landing pad using the RMCE/Bxb1 system. This strategy raised the targeting efficiency by 1.7-fold, and off-target effects were decreased. The miR-21 target genes (Pdcd4 and Atp11b) noticed a significant increase in expression upon the miR-21 sponging through CM21D. Following the expression of CM21D, rCHO cells showed a substantial decrease in doubling time and a 1.3-fold increase in growth rate. Further analysis showed an increased yield of hrsACE2, a secretory recombinant protein, by 2.06-fold. Hence, we can conclude that sponging-induced inhibition of miR-21 may lead to a growth rate increase that could be linked to increased CHO cell productivity. For industrial cell lines, including CHO cells, an increase in productivity is crucial. The results of our research indicate that CM21D is an auspicious CHO engineering approach. KEY POINTS: • CHO is an ideal host cell line for producing industrial therapeutics manufacturing, and miR-21 is downregulated in CHO cells, which produce recombinant proteins. • The miR-21 target genes noticed a significant increase in expression upon the miR-21 sponging through CM21D. Additionally, sponging of miR-21 by CM21D enhanced the growth rate of CHO cells. • Productivity and growth rate were increased in CHO cells expressing recombinant hrs-ACE2 protein after CM21D knocking in.

Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment.

The absence of a definitive cure for amyotrophic lateral sclerosis (ALS) emphasizes the crucial need to explore new and improved treatment approaches for this fatal, progressive, and disabling neurodegenerative disorder. As at the end of 2023, five treatments - riluzole, edaravone, dextromethorphan hydrobromide + quinidine sulfate (DHQ), tofersen, and sodium phenylbutyrate-tauroursodeoxycholic acid (PB-TUDCA) - were FDA approved for the treatment of patients with ALS. Among them PB-TUDCA has been shown to impact DNA processing impairments, mitochondria dysfunction, endoplasmic reticulum stress, oxidative stress, and pathologic folded protein agglomeration defects, which have been associated with ALS pathophysiology. The Phase 2 CENTAUR trial demonstrated significant impact of PB-TUDCA on the ALS Functional Rating Scale-Revised (ALSFRS-R) risk of death, hospitalization, and the need for tracheostomy or permanent assisted ventilation in patients with ALS based on post hoc analyses. More recently, contrasting with the CENTAUR trial results, results from the Phase 3 PHOENIX trial (NCT05021536) showed no change in ALSFRS-R total score at 48 weeks. Consequently, the sponsor company initiated the process with the US FDA and Health Canada to voluntarily withdraw the marketing authorizations for PB-TUDCA. In the present article, we review ALS pathophysiology, with a focus on PB-TUDCA's proposed mechanisms of action and recent clinical trial results and discuss the implications of conflicting trial data for ALS and other neurological disorders.

The comparative effects of bone marrow mesenchymal stem cells and supernatant transplantation on demyelination and inflammation in cuprizone model.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with inflammation and immune dysfunction. OBJECTIVES: We compared the remyelination and immunomodulation properties of mesenchymal stem cells (MSCs) with their conditioned medium (CM) in the cuprizone model. METHODS: Twenty-four C57BL/ 6 mice were divided into four groups. After cuprizone demyelination, MSCs and their CM were injected into the right lateral ventricle of mice. The expression level of IL-1ß, TNF-α, and BDNF genes was evaluated using the qRT-PCR. APC antibody was used to assess the oligodendrocyte population using the immunofluorescent method. The remyelination and axonal repair were studied by specific staining of the LFB and electron microscopy techniques. RESULTS: Transplantation of MSCs and CM increased the expression of the BDNF gene and decreased the expression of IL-1ß and TNF-α genes compared to the cuprizone group, and these effects in the cell group were more than CM. Furthermore, cell transplantation resulted in a significant improvement in myelination and axonal repair, which was measured by luxol fast blue and transmission electron microscope images. The cell group had a higher number of oligodendrocytes than other groups. CONCLUSIONS: According to the findings, injecting MSCs intraventricularly versus cell-conditioned medium can be a more effective approach to improving chronic demyelination in degenerative diseases like MS.

Efficacy of fibroblast transplantation in the healing of cutaneous leishmaniasis scar: A case report.

Autologous fibroblast transplantation has been proven to be a promising method in wound healing with no side effects. This is the first study aimed to determine the efficacy and safety of autologous fibroblast cell injection to the atrophic scar caused by cutaneous leishmaniasis as an endemic disease in many middle-eastern countries. It causes chronic skin lesions and permanently disfiguring scars. Autologous fibroblasts were obtained from the patient's ear skin and were injected intradermally twice at 2-month intervals. Outcomes were measured using ultrasonography, VisioFace, and Cutometer. No adverse reaction was observed. The results showed improvements in epidermal thickness and density, melanin level, and skin lightening. Moreover, the skin elasticity in the scar area increased after the second transplantation. No improvement was observed in dermal thickness and density. A longer follow-up with more patients is recommended to investigate the effectiveness of fibroblast transplantation better.

Masitinib: The promising actor in the next season of the Amyotrophic Lateral Sclerosis treatment series.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with high mortality and morbidity rate affecting both upper and lower motor neurons (MN). Muscle force reduction, behavioral change, pseudobulbar affect, and cognitive impairments are the most common clinical manifestations of ALS. The main physiopathology of ALS is still unclear, though several studies have identified that oxidative stress, proteinopathies, glutamate-related excitotoxicity, microglial activation, and neuroinflammation may be involved in the pathogenesis of ALS. From 1995 until October 2022, only Riluzole, Dextromethorphan Hydrobromide (DH) with Quinidine sulfate (Q), Edaravone, and Sodium phenylbutyrate with Taurursodiol (PB/TUDCO) have achieved FDA approval for ALS treatment. Despite the use of these four approved agents, the survival rate and quality of life of ALS patients are still low. Thus, finding novel treatments for ALS patients is an urgent requirement. Masitinib, a tyrosine kinase inhibitor, emphasizes the neuro-inflammatory activity of ALS by targeting macrophages, mast cells, and microglia cells. Masitinib downregulates the proinflammatory cytokines, indirectly reduces inflammation, and induces neuroprotection. Also, it was effective in phase 2/3 and 3 clinical trials (CTs) by increasing overall survival and delaying motor, bulbar, and respiratory function deterioration. This review describes the pathophysiology of ALS, focusing on Masitinib's mechanism of action and explaining why Masitinib could be a promising actor in the treatment of ALS patients. In addition, Masitinib CTs and other competitor drugs in phase 3 CTs have been discussed.

Risk of autism spectrum disorder in offspring with parental schizophrenia: a systematic review and meta-analysis.

BACKGROUND: The effect of parental schizophrenia on the risk of Autism Spectrum Disorders (ASD) in offspring has been evaluated in previous studies. However, to our knowledge, no systematic review and meta-analysis have assessed this association. In this study, we aimed to evaluate the risk of ASD in offspring with parental schizophrenia. METHODS: The electronic databases EMBASE, PubMed, and Scopus were systematically searched. We administered the Newcastle Ottawa quality assessment scale (NOS) to assess the quality of all selected studies. Combined effect values, as well as their 95% confidence intervals (CI), were calculated. We evaluated heterogeneity using Q and I2 statistics. The publication bias was evaluated by funnel plot and Egger's regression test. In addition, a leave-one-out sensitivity analysis was performed to assess the robustness of the finding. RESULTS: A total of 12 observational studies (10 cohorts and two case-control) were included. Our study found a high risk of ASD in offspring exposed to parental schizophrenia [RR = 2.38 (CI%95 2.0-2.83)]. Subgroup and sensitivity analysis confirmed the robustness of our main analysis. CONCLUSION: The risk of ASD is considerably higher in offspring with parental schizophrenia. Our findings may suggest a shared pathologic pathway between schizophrenia and ASD.

Molecular detection of Crimean-Congo Haemorrhagic Fever (CCHF) virus in hard ticks from South Khorasan, east of Iran.

BACKGROUND & OBJECTIVES: Crimean-Congo Hemorrhagic Fever (CCHF) is a deadly viral infection reported from more than 30 countries. It is considered a zoonosis↱ and tick bites are the main route of transmission in nature. So far, the virus has been identified in 31 species of hard (Ixodidae) and soft (Argasidae) ticks. The aim of this study was to determine the rate of CCHF virus infection in hard ticks from South-Khorasan province, east of Iran. METHODS: In this study, 684 livestock including 302 sheep, 344 goats, 16 cows and 22 camels were sampled from Birjand, Qaen, Khusf, Darmian and Sarbisheh counties. Genus and species of the ticks were diagnosed under stereomicroscope according to valid morphological keys. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the CCHF virus genome based on S segment in 100 ticks. RESULTS: RT-PCR detected CCHF virus genome in 7 out of 100 ticks. Positive ticks belonged to Hyalomma and Rhipicephalus genera. CCHF virus infected species were Rhipicephalus sanguineus, Hyalomma detritium and Hyalomma asiaticum. All the infected ticks were isolated from goat and sheep and were from Birjand county. INTERPRETATION & CONCLUSION: Our results suggest that Hyalomma and Rhipicephalus may be the main vectors of CCHF virus in the study area.

Generating Human Induced Pluripotent Stem Cell Via Low-Dose Polyethylenimine-Mediated Transfection: An Optimized Protocol.

Human dermal fibroblasts (HDFs) can be reprogrammed through different strategies to generate human induced pluripotent stem cells (hiPSCs). However, most of these strategies require high-cost materials and specific equipment not readily accessible in most laboratories. Hence, liposomal and virus-based techniques can replace with polyethylenimine (PEI)-mediated transfection to overcome these challenges. However, few researchers have addressed the PEI's ability to transfect HDFs. This study used PEI reagent to transfer oriP/EBNA1-based vector into HDFs to produce hiPSC lines. We first described conditions allowing the efficient transfection of HDFs with low cytotoxicity and without specific types of equipment and optimized several parameters relevant to the transfection procedure. We then monitored the effect of different N/P ratios on transfection efficiency and cytotoxicity using flow cytometry and fluorescent microscopy. By the results, we found that transfection efficiency was greatly affected by plasmid DNA concentration, PEI concentration, order of combining reagents, serum presence in polyplexes, and the duration of serum starvations. Moreover, using the optimized condition, we found that the N/P ratio of 3 achieved the highest percentage of HDFs positive for green fluorescent protein plasmid (∼40%) with minimal cell toxicity. We finally generated hiPSCs using the optimized protocol and oriP/EBNA1-based vectors. We confirmed hiPSC formation by characterizing tests: alkaline phosphatase staining, immunocytochemistry assay, real-time PCR analysis, in vitro differentiation into three germ layers, and karyotyping test. In conclusion, our results indicated that 25 kDa branched PEI could efficiently transfect HDFs toward generating hiPSCs via a simple, cost-effective, and optimized condition.

Large-scale analysis of MicroRNA expression in motor neuron-like cells derived from human umbilical cord blood mesenchymal stem cells.

Motor neuron diseases such as spinal cord injuries and amyotrophic lateral sclerosis are known as the most common disorders worldwide. Using stem cells (e.g., human umbilical cord blood mesenchymal stem cells) is currently a potent medical approach for modulating the impact of neural damages and regeneration of spinal cord injuries. MicroRNAs (miRNA) are taken into account as principal regulators during differentiation. The miRNAs play a significant role in stem cell self-renewal and fate determination. There are few studies on how miRNAs regulate neural differentiation in stem cells. The purpose of this study is to explore miRNA profiles of CB-MSCs during differentiation into motor neuron-like cells. Human CB-MSCs were isolated and characterized using flow cytometry. Cell differentiation has been induced by combining retinoic acid (RA) and sonic hedgehog (Shh) in a two-step protocol for 14 days. Then, cell differentiation was confirmed by immunocytochemistry and flow cytometry. The miRNA was analyzed using Illumina/Solexa sequencing platform. In this regard, three libraries were prepared to investigate the effect of these two biological morphogens on the miRNA profile of the differentiating cells. These libraries were Control (non-treated CB-MSCs), Test 1 (RA + /Shh +), and Test 2 (RA-/Shh-). Quantitative RT-PCR was employed to verify miRNA expression. CB-MSCs were spindle-shaped in morphology, and they did not express hematopoietic markers. After differentiation, the cells expressed motor neuron markers (i.e., Islet-1, SMI-32, and ChAT) at the protein level after 14 days. The analysis of miRNA sequencing demonstrated a significant up-regulation of miR-9-5p and miR-324-5p in Test 1 (RA + /Shh +). Also, there is a considerable down-regulation of mir-137 and let-7b in Test 2 (RA-/Shh-). These results have been obtained by comparing them with the Control library. Indeed, they were responsible for neuron and motor neuron differentiation and suppression of proliferation in neural progenitor cells. Furthermore, significant up-regulation was detected in some novel microRNAs involved in cholinergic, JAK-STAT, and Hedgehog and MAPK signaling pathways. CB-MSCs are potent to express motor neuron markers. This procedure has been performed by developing a two-week protocol and employing Shh and RA. The miRNA profile analysis showed a significant up-regulation in the expression of some miRs involved in neuron differentiation and motor neuron maturation. MiR-9-5p and miR-324-5p were up-regulated at the early stage of differentiation. Also, miR-137 and miR-let-7b were downregulated in the absence of RA and Shh. Furthermore, several novel miRNAs involved in cholinergic, Hedgehog, MAPK, and JAK-STAT signaling pathways have been detected. However, further studies are still necessary to validate their functions during motor neuron generation and maturation.

In Vitro Assessment of the Gene Expression of EZH-2 and P300 During Motor Neuron Differentiation of Human Umbilical Cord Blood Mesenchymal Stem Cells.

Introduction: Maintenance of neurogenesis depends on the function of some histone-modifying enzymes; including Enhancer of zeste homolog 2 (EZH2) and histone acetyltransferases (P300). The mechanism of epigenetic regulation and gene expression underlying the transition of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) into MNs has not been fully clarified. Methods: Two morphogens; sonic hedgehog (Shh: 100 ng/mL) and retinoic acid (RA: 0.01 mM) were involved in the specification of hUCB-MSCs into MNs after MSC characterization using Flow cytometry. Real time-quantitative PCR and immunocytochemistry were performed to find the expression of the genes at the level of mRNA and protein. Results: The expression of MN-related markers was confirmed at the level of mRNA and protein by induction of differentiation. The results were confirmed by immunocytochemistry and showed those mean cell percentages of 55.33%±15.885% and 49.67%±13.796% could express Islet-1 and ChAT, respectively. The gene expression level of Islet-1 and ChAT was significantly increased in the first and second week of exposure, respectively. After two weeks, the expression level of P300 and EZH-2 genes increased remarkably. No significant expression of Mnx-1 was detected when compared to the control sample. Conclusion: MN-related markers, Islet-1 and ChAT, were detected in differentiated cells of hUCB-MSCs, supporting the potency of cord blood cells in the regeneration of MN-related disorders. Assessing these epigenetic regulatory genes at the protein level can be suggested to confirm their functional epigenetic modifying effects during motor neuron differentiation.

Study on Hard and Soft Ticks of Domestic and Wild Animals in Western Iran.

Background: Ticks are blood-sucking ectoparasites of many vertebrates and act as vectors of a wide range of vector-borne diseases. Alongside pathogens transmission, ticks also cause economic losses in animal industry such as production loss, physical damage, anemia, and poisoning. This study aimed to determine the fauna, geographical distribution and seasonal activity of ticks collected from animals in Lorestan Province, west of Iran. Methods: Ticks were collected from domestic animals including cattle, sheep, goats, chickens, turkeys, pigeons, as well as wild animals such as jackals in 2017-2018. Then, they were identified based on morphological characteristics using valid identification keys. Results: Out of a total of 706 ticks, 433 (61.33%), 104 (14.73%), 33 (4.67%) and 136 (19.26%) ticks were collected in spring, summer, autumn and winter, respectively. In terms of hard ticks, 4 genera and 6 species were identified: Hyalomma asiaticum (22.80%), Hyalomma anatolicum (3.68%), Hyalomma marginatum (2.40%), Rhipicephalus sanguineus (0.84%), Dermacentor marginatus (1.13%), and Haemaphysalis sulcata (0.64%). Additionally, two genera and four species fell into soft ticks: Argas persicus (60.48%), Argas reflexus (6.65%), Ornithodoros canstrini (0.70%) and Ornithodoros erraticus (0.42%). There was significant variation in the seasonal activity and abundance of ticks in different seasons but in the tick abundancy among different regions. Conclusion: The present study provides a perspective of the distribution status of ticks in Lorestan Province, their seasonal activity and the likelihood of emergence of related diseases.

Differentiation of Mesenchymal Stem Cells Derived From Human Adipose Tissue Into Cholinergic-like Cells: An in Vitro Study.

INTRODUCTION: Cholinergic-associated diseases currently constitute a significant cause of neurological and neurodegenerative disabilities. As the drugs are not efficient in improving the suffered tissues, stem cell treatment is considered an effective strategy for substituting the lost cells. METHODS: In the current study, we set out to investigate the differentiation properties of human Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) into cholinergic-like cells by two morphogens of Retinoic Acid (RA) and Sonic Hedgehog (Shh) using a three-step in vitro procedure. The results were evaluated using real-time PCR, flow cytometry, and immunocytochemistry for two weeks. RESULTS: Our data showed that the cells could express cholinergic specific markers, including Islet-1, Acetylcholinesterase (AChE), SMI-32, and Nestin, at mRNA and protein levels. We could also quantitatively evaluate the expression of Islet-1, AChE, and Nestin at 14 days post-induction using flow cytometry. CONCLUSION: Human AD-MSCs are potent cells to differentiate into cholinergic-like cells in the presence of RA and Shh through a three-step protocol. Thus, they could be a suitable cell candidate for the regeneration of cholinergic-associated diseases. However, more functional and electrophysiological analyses are needed in this regard.

Fabrication of chitosan/agarose scaffolds containing extracellular matrix for tissue engineering applications.

One of the most effective approaches for treatment of cartilage involves the use of porous three-dimensional scaffolds, which are useful for improving not only cellular adhesion but also mechanical properties of the treated tissues. In this study, we manufactured a composite scaffold with optimum properties to imitate nasal cartilage attributes. Cartilage extracellular matrix (ECM) was used in order to improve the cellular properties of the scaffolds; while, chitosan and agarose were main materials that are used to boost the mechanical and rheological properties of the scaffolds. Furthermore, we explored the effect of the various weight ratios of chitosan, agarose, and ECM on the mechanical and biomedical properties of the composite scaffolds using the Taguchi method. The resulting composites display a range of advantages, including good mechanical strength, porous morphology, partial crystallinity, high swelling ratio, controlled biodegradability rate, and rheological characteristics. Additionally, we performed the cytotoxicity tests to confirm the improvement of the structure and better cell attachments on the scaffolds. Our findings illustrate that the presence of the ECM in chitosan/agarose structure improves the biomedical characteristics of the final scaffold. In addition, we were able to control the mechanical properties and microstructure of the scaffolds by optimizing the polymers' concentration and their resulting interactions. These results present a novel scaffold with simultaneously enhanced mechanical and cellular attributes comparing to the scaffolds without ECM for nasal cartilage tissue engineering applications.

Hypothalamic-Pituitary-Gonadal Activity in Paradoxical and Psychophysiological Insomnia.

BACKGROUND: Although insomnia is a sex-dimorphic disorder, there is limited knowledge about the association between sex hormones and insomnia. In the present study, the level of hypothalamus-pituitary-gonadal (HPG) axis activity was investigated in patients with insomnia by measuring serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), 17α-Hydroxyprogesterone, testosterone, progesterone, estradiol, dehydroepiandrosterone sulfate, and sex hormone-binding globulin. METHODS: Numbers of 19 patients; including 13 females (68.40%) with paradox insomnia (32-53 years; 43.20 ± 6.40) and 17 patients; including 8 females (47.05%) with psychophysiological insomnia (14-62 years; 38.40 ± 16.30) were recruited. Seventeen aged-matched normal sleeper consisted of 13 males (26-59 years; 40.70 ± 10) consisted of 13 males (76.50%) were also recruited as control group. Insomnia was diagnosed by a sleep clinician according to the International Classification of Sleep Disorders-Second Edition criteria and an overnight polysomnography (PSG). A volume of 5 ml of venous blood samples were collected, prepared, and stored at 8 AM under standard condition. Serum levels of hormones were measured using enzyme-linked immunosorbent assay kits. Data were analyzed by Chi-square and ANCOVA. The associations between PSG and biochemical parameters were evaluated using multiple linear regression analysis. RESULTS: There were no significant differences in all biochemical analyses between two insomnia subgroups (paradoxical and psychophysiological insomnia) and normal sleepers. Testosterone was positively related to maximum pulse transit time (PTT). Moreover, both LH and FSH were positively related to wake index and diastolic blood pressure. CONCLUSION: Although there were no significant differences in all HPG's hormones between groups, both LH and FSH were associated with wake index and diastolic blood pressure. Moreover, testosterone was positively related to PTT.

Evaluation of cellular attachment and proliferation on different surface charged functional cellulose electrospun nanofibers.

Fabrication and characterization of different surface charged cellulose electrospun scaffolds including cellulose acetate (CA), cellulose, carboxymethyl cellulose (CMC) and quaternary ammonium cationic cellulose (QACC) for biomedical applications have been reported in this research. Several instrumental techniques were employed to characterize the nanofibers. MTT assay and cell attachment studies were also carried out to determine the cytocompatibility, viability and proliferation of the scaffolds. Fabricated CA, cellulose, CMC and QACC nanofibers had 100-600 nm diameter, -9, -1.75, -12.8, + 22 mV surface potential, 2.5, 4.2, 7.2, 7 MPa tensile strength, 122, 320, 515, 482 MPa Young modules, 430, 530, 670 and 642% water uptake and 92°, 58°, 45°, 47° contact angle respectively. The findings showed that cell adhesion and proliferation is strongly enhanced on the modified surfaces with quaternary ammonium and carboxymethyl groups. We believe the use of cationic and anionic surface modified cellulose electrospun nanofibers presents promising materials for biomedical applications.

Correction to: Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.

The original version of this article unfortunately contained mistake in the affiliation. Affiliation 1 should be read as "Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran". The original article has been corrected.

Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.

A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer's disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. Graphical Abstract ᅟ.

Intrahippocampal Transplantation of Undifferentiated Human Chorionic- Derived Mesenchymal Stem Cells Does Not Improve Learning and Memory in the Rat Model of Sporadic Alzheimer Disease.

BACKGROUND AND OBJECTIVE: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with consequent cognitive impairment and behavioral deficits. AD is characterized by loss of cholinergic neurons and the presence of beta-amyloid protein deposits. Stem cell transplantation seems to be a promising strategy for regeneration of defects in the brain. METHOD: One of the suitable type of stem cells originated from fetal membrane is Chorion-derived Mesenchymal Stem Cells (C-MSCs). MSCs were isolated from chorion and characterized by Flowcytometric analysis. Then C-MSCs labeled with DiI were transplanted into the STZ induced Alzheimer disease model in rat. RESULTS: Nissl staining and behavior test were used to assess the efficacy of the transplanted cells. Phenotypic and Flowcytometric studies showed that isolated cells were positive for mesenchymal stem cell marker panel with spindle like morphology. CONCLUSION: Learning and memory abilities were not improved after stem cell transplantation. C-MSCs transplantation can successfully engraft in injured site but the efficacy and function of transplanted cells were not clinically satisfied.

Histologic and Histomorphometric Assessment of Xenograft Bone Substitute versus Synthetic Nonceramic Hydroxyapatite for Canine Tooth-Socket Preservation.

This study sought to histologically and histomorphometrically assess and compare application of xenograft bone substitute and synthetic nonceramic hydroxyapatite for tooth-socket preservation in dogs. This split-mouth clinical trial was conducted in five hybrid dogs, using four tooth sockets in each dog, with a total of 20 sockets for evaluation. Group 1 received xenografts, and group 2 received synthetic nonceramic hydroxyapatite in the sockets. In group 3 (positive controls), sockets remained empty. All sockets were covered with collagen resorbable membrane, and the flap was stitched using nonresorbable sutures. In group 4 (negative control), sockets were without membrane, left empty, and sutured. After 12 wk, 8-mm-high bone core biopsies were harvested from inside the sockets, using a trephine bur with an internal diameter of 2 mm. We assessed the tissue in terms of percentage of newly formed viable bone, percentage of remaining particles, degree of inflammation, and type of connective tissue. Data were statistically analyzed. The percentage of newly formed viable bone was 34.98% in group 1 and 41.30% in group 2, and this difference was not statistically significant (p = 0.710). The percentage of remaining particles was 15.95% in group 1 and 14.14% in group 2; this difference was also not statistically significant (p = 0.902). Both synthetic nonceramic hydroxyapatite and xenograft bone substitute showed similar efficacy, histologically and histomorphometrically, when used with resorbable collagen membrane for tooth-socket preservation in dogs.