Sex hormone therapy in Multiple Sclerosis: A systematic review of randomized clinical trials.

Background: In spite of the observed immunomodulatory properties of different sex hormones on Multiple Sclerosis (MS) in different investigations, to date, there has been no study to systematically review the documents to add more powerful data to the field. Objectives: Therefore, in this paper we aim to systematically review clinical and randomized controlled trials (RCT) assessing the effect of sex hormone therapies on individuals with MS. Design: A comprehensive search of electronic databases including PubMed, EMBASE, and Scopus was conducted. Clinical trials and RCTs that assessed the impact of sex hormones on individuals with MS were selected and included in the systematic review. Data sources and methods: In the final phase of the search strategy, 9 papers reached the criteria for entering in the systematic review. Two independent reviewers extracted the relevant data from each article according to the standardized data extraction form. Two reviewers also assessed the quality of each study independently using PEDro scale. Results: We categorized three different classifications of outcomes including clinical, MRI, and immune system findings and put each measured outcome in the category which matched best. Conclusion: In conclusion, the existed investigations on the effect of sex hormones on inflammatory and neurodegenerative components of MS are promising particularly in relapsing-remitting MS (RRMS).

Immunomodulatory properties of different sex hormones on Multiple Sclerosis (MS) have been proposed. Therefore, in this paper we aim to systematically review clinical and randomized controlled trials (RCT) assessing the effect of sex hormone therapies on individuals with MS. A comprehensive search of electronic databases was conducted. Clinical trials and RCTs that assessed the impact of sex hormones on individuals with MS were selected and included in the systematic review. In the final phase of the search strategy, 9 papers reached the criteria for entering in the systematic review. Two independent reviewers extracted the relevant data from each article according to the standardized data extraction form. We categorized three different classifications of outcomes including clinical, MRI, and immune system findings and put each measured outcome in the category which matched best. The existed investigations on the effect of sex hormones on inflammatory and neurodegenerative components of MS are promising particularly in relapsing-remitting MS (RRMS).

Subcutaneous Injection of Allogeneic Adipose-Derived Mesenchymal Stromal Cells in Psoriasis Plaques: Clinical Trial Phase I.

OBJECTIVE: Mesenchymal stromal cells (MSCs) play immunomodulatory role in various autoimmune diseases. Previous pre-clinical and clinical studies have shown that MSCs could be a therapeutic modality for psoriasis. However, the mechanisms of treatment and its possible side effects are under investigation. In this study, the safety and probable efficacy of injecting allogeneic adipose-derived mesenchymal stromal cells (ADSCs) in psoriatic patients were evaluated. MATERIALS AND METHODS: In this phase I clinical study with six months of follow-up, total number of 1×106 or 3×106 cells/cm2 of ADSCs were injected into the subcutaneous tissue of each plaque as a single dose in three males and two females (3M/2F) with a mean age of 32.8 ± 8.18. The primary outcome was safety. Changes in clinical and histological indexes, the number of B and T lymphocytes in local and peripheral blood, and serum levels of inflammatory cytokines were assessed. Paired t test was used to compare variables at two time points (baseline and six months after injection) and repeated measures ANOVA test was utilized for variables at three time points in follow-up visits. RESULTS: No major adverse effects such as burning, pain, itching, or any systemic side effects were observed following ADSCs injection, and the lesions showed slight to considerable improvement after injection. The mRNA expression levels of pro-inflammatory factors were reduced in the dermis of the patients after injection. The increased expression level of Foxp3 transcription factor in the patient blood samples suggested modulation of inflammation after ADMSCs administration. Six months after the intervention, no major side effects were reported, but skin thickness, erythema, and scaling of the plaques, as well as the PASI score, were decreased in majority of patients. CONCLUSION: Our study suggested that ADSC injection could be considered as a safe and effective therapeutic approach for psoriatic plaques (registration number: IRCT20080728001031N24).

Intravenous transplantation of bone marrow-derived mesenchymal stromal cells in patients with multiple sclerosis, a phase I/IIa, double blind, randomized controlled study.

Multiple sclerosis (MS) is a progressive, demyelinating neurodegenerative disease of the central nervous system. MS is immune-mediated and leads to disability especially in young adults. Even though 18 MS therapy drugs were approved, they slightly inhibit disease progression and do not induce regeneration and repair in the nervous system. Mesenchymal stromal cells (MSCs) have emerged as a new therapeutic modality in regenerative medicine and tissue engineering due to their immunomodulation and bio regenerative properties. We have designed a randomized, controlled clinical trial to assess safety and possible efficacy of MSC application in MS patients. Twenty-one MS patients were enrolled. Patients were allocated in two distinct groups: treatment group, which received systemic transplantation of autologous bone marrow-derived MSCs, and control group, which received placebo at the first injections. Patients in control group received MSCs at the second injection while the treatment group received placebo. All the patients were followed for 18 months. Follow-ups included regular visits, laboratory evaluation, and imaging analysis. Control patients received MSCs six month after treatment group. No severe immediate or late adverse events were observed in both groups after interventions. We did not find any significant differences in the rate of relapses, Expanded Disability Status Scale (EDSS) score, cognitive condition, Magnetic Resonance Imaging (MRI) findings, or any biomarkers of cerebrospinal fluid between the two groups and in each group before and after cell infusion. Transplantation of autologous bone marrow-derived mesenchymal stromal cells is safe and feasible. The efficacy of transplantation of these cells should be evaluated through designing randomized clinical trials with larger sample sizes, different administration routes, other cell types (allogeneic adipose derived MSCs, allogeneic Wharton's jelly derived MSCs …), repeated injections, and longer follow-up periods.

Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial.

BACKGROUND: Intra-articular injection of mesenchymal stromal cells (MSCs) with immunomodulatory features and their paracrine secretion of regenerative factors proposed a noninvasive therapeutic modality for cartilage regeneration in knee osteoarthritis (KOA). METHODS: Total number of 40 patients with KOA enrolled in two groups. Twenty patients received intra-articular injection of 100 × 106 allogeneic adipose-derived mesenchymal stromal cells (AD-MSCs), and 20 patients as control group received placebo (normal saline). Questionnaire-based measurements, certain serum biomarkers, and some cell surface markers were evaluated for 1 year. Magnetic resonance imaging (MRI) before and 1 year after injection was performed to measure possible changes in the articular cartilage. RESULTS: Forty patients allocated including 4 men (10%) and 36 women (90%) with average age of 56.1 ± 7.2 years in control group and 52.8 ± 7.5 years in AD-MSCs group. Four patients (two patients from AD-MSCs group and two patients from the control group) excluded during the study. Clinical outcome measures showed improvement in AD-MSCs group. Hyaluronic acid and cartilage oligomeric matrix protein levels in blood serum decreased significantly in patients who received AD-MSCs (P < 0.05). Although IL-10 level significantly increased after 1 week (P < 0.05), the serum level of inflammatory markers dramatically decreased after 3 months (P < 0.001). Expressions of CD3, CD4, and CD8 have a decreasing trend during 6-month follow-up (P < 0.05), (P < 0.001), and (P < 0.001), respectively. However, the number of CD25+ cells increased remarkably in the treatment group 3 months after intervention (P < 0.005). MRI findings showed a slight increase in the thickness of tibial and femoral articular cartilages in AD-MSCs group. The changes were significant in the medial posterior and medial anterior areas of ​​the tibia with P < 0.01 and P < 0.05, respectively. CONCLUSION: Inter-articular injection of AD-MSCs in patients with KOA is safe. Laboratory data, MRI findings, and clinical examination of patients at different time points showed notable articular cartilage regeneration and significant improvement in the treatment group. TRIAL REGISTRATION: Iranian registry of clinical trials (IRCT, https://en.irct.ir/trial/46 ), IRCT20080728001031N23. Registered 24 April 2018.

Advanced Therapy Medicinal Products in Vitiligo; Current Status, Future Prospect, and Approved Treatments.

Vitiligo is an auto-immune disease, causing depigmentation of skin in 0.2-1.8% of global population. Topical corticosteroids and calcineurin inhibitors are the only treatments with firm evidence of optimal effectiveness with considerable side effects. Phototherapies might not induce serious side effects, although the effectiveness of the method is limited. Advanced therapy medicinal products (ATMPs) are emerging treatment modalities based on correction and replacement of affected genes, damaged tissues or cells in treatment of difficult-to-treat diseases. Due to optimal effectiveness and minimal side effects, ATMPs have recently gained much attention in order to develop new treatments. In this review, the ATMPs for treating vitiligo were along with its clinical success, affordability and cost-effectiveness. Currently, the main ATMP based products using in treatment of vitiligo are non-cultured epidermal cell, melanocytes, and hair follicle melanocytes. These products have shown promising results in the non-responding vitiligo patients. Furthermore, mesenchymal stem cells and multi-lineage differentiating stress enduring cells are other new potential modalities. Recently, Iranian Food and Drug Administration (IR-FDA) authorized the first cell-based product for vitiligo. This product is autologous suspension of keratinocytes and melanocytes. Although ATMPs are efficient and could be cost-effective in long term, the most important obstacle is affordability of them. This could be facilitated by insurance companies and instalments payment programs from manufacturers.

COVID-19 Vaccination Willingness and Acceptability in Multiple Sclerosis Patients: A Cross Sectional Study in Iran.

Multiple sclerosis (MS) is a chronic, predominantly immune-mediated degenerative disease of the central nervous system. Due to prolonged use of immunomodulatory and immunosuppressive medications, vaccine hesitancy could be common among MS patients. Our main aim in the current study was to evaluate the willingness and acceptability of COVID-19 vaccination in patients with MS. In our multicenter cross-sectional questionnaire-based clinical study, 892 patients completed the questionnaire between May to June 2021. The questionnaire consisted of demographic data, MS disease-related factors, history of COVID-19 infection/vaccination, and any existing comorbidities. Statistical analysis was performed using SPSS software version 19. Overall, 68% of the participants expressed willingness to be vaccinated. Major causes of vaccine refusal in our patients were the fear of reducing the efficacy of disease modifying drugs (DMDs) upon vaccination as well as distrusting the vaccines and overestimation bias in the power of their innate immunity and potential COVID-19 resistance. Some demographic factors affected vaccination enthusiasm in our study. Our findings did not show significant correlation between the age and comorbidity and vaccine willingness. Only one-third of our patients received their vaccine information from healthcare providers. The majority of them received these data from official broadcasting channels and social media. However, despite several concerns, the willingness of COVD-19 vaccination in the Iranian MS patients is remarkable.

Evaluation of the Shear Bond Strength and Antibacterial Activity of Orthodontic Adhesive Containing Silver Nanoparticle, an In-Vitro Study.

This study evaluated the effect of incorporating silver nanoparticles (AgNPs) into conventional orthodontic adhesive on its antibacterial activity and the shear bond strength (SBS) to stainless steel orthodontic brackets. Thirty-four extracted premolars were randomly allocated into two groups (n = 17). Orthodontic adhesive (Transbond XT, 3M Unitek) was blended with AgNPs (50 nm, 0.3% w/w) to form a nano-adhesive. In order to bond stainless steel twin brackets (0.022-inch, American Orthodontics), Transbond XT (n = 17) and nano-adhesive (n = 17) were used in each group, respectively, after acid etching (37% phosphoric acid, 30 s) and rinsing with water (15 s). SBS and the adhesive remnant index (ARI) scores were recorded. Antibacterial activity against Streptococcus mutans in both groups after 24 h and 30 days was assessed (Disc agar diffusion test) and the inhibition zone diameter around each specimen was measured and recorded. Adding AgNPs significantly (p = 0.009) reduced the mean (SD) SBS in the nano-adhesive group [10.51(7.15) MPa] compared to Transbond XT [17.72(10.55) MPa]. The ARI scores on the Transbond XT and nano-adhesive showed no statistically significant difference (p = 0.322). Nano-adhesive with AgNPs showed significant antibacterial activity against Streptococcus mutans at 24 h and 30 days (p < 0.001). In both groups, no significant decline in the zones of inhibition was detected after 30 days (p = 0.907). The findings suggest that SBS decreased after incorporation of AgNPs [0.3% (w/w)], but was still above the recommended SBS of 5.9-7.8 MPa. The nano-adhesive showed significant antibacterial activity which did not change much after 30 days.

Autologous bone marrow-derived CD133 cells with core decompression as a novel treatment method for femoral head osteonecrosis: a pilot study.

BACKGROUND: Avascular necrosis (AVN) of femoral head is a progressive bone disease due to ischemia of femoral head; patients experience pain and they can not do normal activity. There is not an effective way to treat the cause of this disease. In recent studies, treatment of this disease using pluripotent stem cell-derived mesenchyme is safe and effective, but this method needs more investigation. In this study, the safety and efficacy of CD133+ cells were evaluated as a novel method of stem cell therapy to treat AVN. METHODS: In this prospective quasi-experimental study, the participants were selected among patients with AVN who were referred to the Royan Cell Therapy Center. Autologous bone marrow-derived CD133+ cells were injected into the necrotic site of the femoral head during core decompression (CD). The Visual Analogue Scale (VAS), Harris Hip Score (HHS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) and walking distance (WD) were measured before and 2, 6 and 12 months after CD. RESULTS: Overall, nine patients (six men and three women) were investigated in this study. Their mean age was 26 years old. All of them significantly improved in VAS, HHS, WOMAC and WD scores and they could do more activity without pain. Also, imaging findings demonstrated significant reductions in joint injuries. Significant complications were not seen in patients. DISCUSSION: This prospective quasi-experimental study demonstrated that, in patients with AVN, a single bone marrow-derived CD133+ cell injection into the necrotic site of the femoral head during CD is safe and effective in providing significant, clinically relevant pain relief and patients could do more activity over 2, 6 and 12 months. This pilot study suggested further clinical trials over an extended assessment period to approve bone marrow-derived CD133+ cell injection to treat AVN.