Background Cell-free Mesenchymal stromal cells (MSCs) have been considered due to their capacity to modulate the immune system and suppress cytokine storms caused by SARS-CoV-2. This prospective randomized double-blind placebo-controlled clinical trial aimed to assess the safety and efficacy of secretome derived from allogeneic menstrual blood stromal cells (MenSCs) as a treatment in patients with severe COVID-19. Methods Patients with severe COVID-19 were randomized (1:1) to either MenSC-derived secretome treatment or the control group. Subjects received five intravenous infusions of 5 mL secretome or the same volume of placebo for five days and were monitored for safety and efficacy for 28 days after treatment. Adverse events, laboratory parameters, duration of hospitalization, clinical symptom improvement, dynamic of O2 saturation, lymphocyte number, and serial chest imaging were analyzed. Results All safety endpoints were observed without adverse events after 72 h of secretome injection. Within 28 days after enrollment, 7 patients (50%) were intubated in the treated group versus 12 patients (80%) in the control group. Overall, 64% of patients had improved oxygen levels within 5 days of starting treatment (P < 0.0001) and there was a survival rate of 57% in the treatment group compared to 28% in the control group was (P < 0.0001). Laboratory values revealed that significant acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. Significant improvement in lymphopenia was associated with an increase in mean CD4+ and CD8+ lymphocyte counts of 20% (P = 0.06) and 15% (P < 0.05), respectively. Following treatment, percentage of pulmonary involvement showed a significant improvement in the secretome group (P < 0.0001). This improvement differed significantly between survivors and those who were dying (P < 0.005). Conclusions For the first time, this study demonstrated that in hospitalized patients with severe COVID-19, therapy with MenSCs-derived secretome leads to reversal of hypoxia, immune reconstitution, and downregulation of cytokine storm, with no adverse effects attributable to the treatment. Given these outcomes, it may be possible to use this type of treatment for serious inflammatory lung disease with a mechanism similar to COVID-19 in the future. However, it is necessary to evaluate the safety and efficacy of MenSCs-derived secretome therapy in clinical trials on a larger population of patients. Trial registration: ClinicalTrials.gov Identifier: NCT05019287. Registered 24AGUEST 2021, retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05019287. IRCT, IRCT20180619040147N6. Registered 04/01/2021.

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BackgroundThe peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. Several studies have demonstrated a significant association between Pro12Ala polymorphism of the PPAR­γ2 gene and metabolic disorders. Therefore, this study aimed to evaluate the association of Pro12Ala polymorphism with increased risk of NAFLD in Iranian patients with type 2 diabetes mellitus.MethodsThis cross-sectional study was performed on 145 healthy control subjects and 145 NAFLD patients with a history of type 2 diabetes. Pro12Ala polymorphism genotyping was performed using PCR–restriction fragment length polymorphism (RFLP) technique with the Bs1I restriction enzyme.ResultsOur results demonstrated that CC and GG genotypes of Pro12Ala were found in the participants, but there was no statistically significant difference between NAFLD patients and healthy controls (P = 0.64 and χ2 = 0.21).ConclusionThis study suggests that Pro12Ala polymorphism of the PPAR­γ2 gene cannot be considered as a risk factor for NAFLD in the Iranian population.

Background The major obstacle associated with assisted reproduction is poor ovarian response (POR) to controlled ovarian stimulation. Consequently, mesenchymal stem cell therapy has been proposed as a potential treatment for female infertility and/or restoration of ovarian function in POR women. The initial phase of the study showed an increase in pregnancy rate for women with POR who received menstrual blood-derived-mesenchymal stromal cells (MenSCs) into their ovaries. The objective was to evaluate whether this treatment could improve ovarian reserve parameters and pregnancy outcome in a larger population with POR. Method This study included 180 infertile individuals with reduced ovarian reserve who declined oocyte donation. The participants were separated into two groups according to their preference: those who received bilateral MenSCs intraovarian injection and those who did not receive any intervention. These two groups were further divided into two age categories (≤ 40 years and > 40 years). The primary outcomes assessed included a comparison of serum FSH, AMH, and AFC levels pre- and post-treatment. Secondary outcomes evaluated were the quantity and quality of oocytes and embryos, biochemical/clinical pregnancy rates, live birth rates. Results The treatment of MenSCs was found to be generally well-tolerated and free of safety issues. At the 2-4-month follow-up, there was a significant improvement in AMH (P = 0.0007) and AFC (P < 0.001) among the women treated with MenSCs, while the control group experienced a notable decrease in these values (P < 0.0001 and P < 0.001, respectively). A subgroup analysis based on age (≤ 40 years) revealed that 12 (27.3%) patients in the MenSCs group and just 2 (4.5%) patients in the control group had spontaneous pregnancies within 3 to 4 months (P = 0.003). Similarly, 8 people from the MenSCs group (27.6%) and 2 from the control group (4.8%) became pregnant after ICSI (P = 0.009). Conclusion The injection of MenSCs is an efficacious and safe methodology to improve markers of low ovarian reserve, particularly in women aged forty or younger. This treatment has been found to significantly increase the number and quality of oocytes, the embryo quality, the fertilization rate, and the pregnancy rate, particularly spontaneous pregnancies, and boost the live birth rate. Trial registration: ClinicalTrials.gov Identifier: NCT05703308. Registered 01/26/2023, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05703308. IRCT, IRCT20180619040147N4. Registered 08/01/2020.