A Roadmap for the Production of a GMP-Compatible Cell Bank of Allogeneic Bone Marrow-Derived Clonal Mesenchymal Stromal Cells for Cell Therapy Applications

Background: Allogeneic mesenchymal stromal cells (MSCs) have been used extensively in various clinical trials. Nevertheless, there are concerns about their efficacy, attributed mainly to the heterogeneity of the applied populations. Therefore, producing a consistent population of MSCs is crucial to improve their therapeutic efficacy. This study presents a good manufacturing practice (GMP)-compatible and cost-effective protocol for manufacturing, banking, and lot-release of a homogeneous population of human bone marrow-derived clonal MSCs (cMSCs). Methods: Here, cMSCs were isolated based on the subfractionation culturing method. Afterward, isolated clones that could reproduce up to passage three were stored as the seed stock. To select proliferative clones, we used an innovative, cost-effective screening strategy based on lengthy serial passaging. Finally, the selected clones re-cultured from the seed stock to establish the following four-tired cell banking system: initial, master, working, and end of product cell banks (ICB, MCB, WCB, and EoPCB). Results: Through a rigorous screening strategy, three clones were selected from a total of 21 clones that were stored during the clonal isolation process. The selected clones met the identity, quality, and safety assessments criteria. The validated clones were stored in the four-tiered cell bank system under GMP conditions, and certificates of analysis were provided for the three-individual ready-to-release batches. Finally, a stability study validated the EoPCB, release, and transport process of the frozen final products. Conclusion: Collectively, this study presents a technical and translational overview of a GMP-compatible cMSCs manufacturing technology that could lead to the development of similar products for potential therapeutic applications. Graphical Abstract: [Figure not available: see fulltext.

Nonordered dendritic mesoporous silica nanoparticles as promising platforms for advanced methods of diagnosis and therapies

Dendritic mesoporous silica nanoparticles (DMSNs) are a new generation of porous materials that have gained great attention compared to other mesoporous silicas due to attractive properties, including straightforward synthesis methods, modular surface chemistry, high surface area, tunable pore size, chemical inertness, particle size distribution, excellent biocompatibility, biodegradability, and high pore volume compared with conventional mesoporous materials. The last years have witnessed a blooming growth of the extensive utilization of DMSNs as an efficient platform in a broad spectrum of biomedical and industrial applications, such as catalysis, energy harvesting, biosensing, drug/gene delivery, imaging, theranostics, and tissue engineering. DMSNs are considered great candidates for nanomedicine applications due to their ease of surface functionalization for targeted and controlled therapeutic delivery, high therapeutic loading capacity, minimizing adverse effects, and enhancing biocompatibility. In this review, we will extensively detail state-of-the-art studies on recent advances in synthesis methods, structure, properties, and applications of DMSNs in the biomedical field with an emphasis on the different delivery routes, cargos, and targeting approaches and a wide range of therapeutic, diagnostic, tissue engineering, vaccination applications and challenges and future implications of DMSNs as cuttingedge technology in medicine

Nonordered dendritic mesoporous silica nanoparticles as promising platforms for advanced methods of diagnosis and therapies

Dendritic mesoporous silica nanoparticles (DMSNs) are a new generation of porous materials that have gained great attention compared to other mesoporous silicas due to attractive properties, including straightforward synthesis methods, modular surface chemistry, high surface area, tunable pore size, chemical inertness, particle size distribution, excellent biocompatibility, biodegradability, and high pore volume compared with conventional mesoporous materials. The last years have witnessed a blooming growth of the extensive utilization of DMSNs as an efficient platform in a broad spectrum of biomedical and industrial applications, such as catalysis, energy harvesting, biosensing, drug/gene delivery, imaging, theranostics, and tissue engineering. DMSNs are considered great candidates for nanomedicine applications due to their ease of surface functionalization for targeted and controlled therapeutic delivery, high therapeutic loading capacity, minimizing adverse effects, and enhancing biocompatibility. In this review, we will extensively detail state-of-the-art studies on recent advances in synthesis methods, structure, properties, and applications of DMSNs in the biomedical field with an emphasis on the different delivery routes, cargos, and targeting approaches and a wide range of therapeutic, diagnostic, tissue engineering, vaccination applications and challenges and future implications of DMSNs as cutting-edge technology in medicine

Investigation of shear reinforcement for reinforced concrete flat slabs

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN013620 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Comparative effect of different concentrations of hydro-ethanolic extract of chamomile on freeze-thawn semen quality of rams

Oxidative stress during freeze-thawing process causes reduction in motility, viability, membrane functions and finally sperm fertility. The aim of this study was to determine the effect of Chamomile extract as natural antioxidant on quality of cryopreserved ram sperm. In this study semen was collected from five mature rams twice a week using an artificial vagina and the ejaculates were pooled equally in order to eliminate the individual effects. Different levels of extract of Chamomile (0, 50, 66.66, 100 and 200 ml/dl of diluent solution) were added to diluent based tris-egg yolk. After cooling, filling and sealing of the samples, they were frozen with nitrogen vapor and immersed in liquid nitrogen and were stored until evaluation time. After thawing, results showed that addition of 66.66 ml/dl of extract increased total motility, progressive motility, curvilinear velocity, straight–line velocity, linearity, viability and plasma membrane integrity of sperm compared to the control and other treatment groups (

Randomized controlled trial of astaxanthin impacts on antioxidant status and assisted reproductive technology outcomes in women with polycystic ovarian syndrome

Purpose: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women, is typically accompanied by a defective oxidative defense system. Here, we investigated the effect of astaxanthin (AST) as a powerful antioxidant on the oxidative stress (OS) response and assisted reproductive technology (ART) outcomes in PCOS patients. Methods: In this double-blind, randomized, placebo-controlled trial, PCOS patients were randomly assigned into two groups. The intervention group received 8 mg AST, and the control group received the placebo daily for 40 days. The primary outcomes were the serum and follicular fluid (FF) levels of the OS biomarkers and the expression levels of the specific genes and proteins in the oxidative stress response pathway. The secondary outcomes were considered ART outcomes. Results: According to our findings, a 40-day course of AST supplementation led to significantly higher levels of serum CAT and TAC in the AST group compared to the placebo group. However, there were no significant intergroup differences in the serum MDA and SOD levels, as well as the FF levels of OS markers. The expression of Nrf2, HO-1, and NQ-1 was significantly increased in the granulosa cells (GCs) of the AST group. Moreover, the MII oocyte and high-quality embryo rate were significantly increased in the AST group compared to the placebo group. We found no significant intergroup difference in the chemical and clinical pregnancy rates. Conclusion: AST treatment has been shown to increase both serum TAC levels and activation of the Nrf2 axis in PCOS patients� GCs. Trial Registration: ClincialTrials.gov Identifier: NCT03991286. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

Antioxidant supplementations ameliorate PCOS complications: a review of RCTs and insights into the underlying mechanisms

Polycystic ovary syndrome (PCOS) is one of the most important gynecological disorders of women in the age of reproduction. Different hormonal and inflammatory cross-talks may play in the appearance of its eventual complications as a leading cause of infertility. Excessive production of reactive oxygen species over the power of the antioxidant system as oxidative stress is known to contribute to a variety of diseases like PCOS. Thus, the utilization of antioxidants can be efficient in preventing or assistant in treating these diseases. In this review, we describe the clinical trial studies that have examined the efficiency of antioxidant strategies against PCOS and the possible underlying mechanisms. The investigations presented here lead us to consider that targeting oxidative stress pathways is probably a powerful promising therapeutic approach towards PCOS. There is preparatory evidence of the effectiveness of antioxidant interventions in ameliorating some of the PCOS complications, including metabolic and hormonal disorders. Due to limited data and relatively few clinical trials, many of these interventions need further investigation before they can be considered effective agents for routine clinical use. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature