Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with an array of acute and chronic diseases, in humans. However, their specific effects on the stem cells remain unclear. Here, we report the effects of PM collected from Jeddah city on bone marrow mesenchymal stem cells (BM-MSCs) on proliferation, cell death, related gene expression and systems biological analysis aiming to understand the underlying mechanisms. Two different sizes (PM_2.5-₁₀) were tested in vitro at various concentrations (15 to 300 µg/ml) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM_2.5 increased BM-MSCs proliferation, while higher concentrations decreased it. PM₁₀ decreased BM-MSCs proliferation in a concentration-dependant manner. The X-Ray Fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses showed that heavy metals were associated with signalling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential regulation of the apoptosis genes (BCL2, BAX); upregulation of inflammation associated genes (TNF-a and IL-6) and downregulation of cell cycle regulation gene (P53). We conclude that PM could affect different cellular functions and predispose to debilitating diseases.

Fractures are the most common large organ trauma in humans. The initial inflammatory re-sponse promotes bone healing during the initial post-fracture phase, but chronic and persistent inflammation due to infection or other factors does not contribute to the healing process. The precise mechanisms by which immune cells and their cytokines are regulated in bone healing remain unclear. The use of mesenchymal stem cells (MSCs) for cellular therapy of bones injury is a novel clinical treatment approach. Bone progenitor MSCs not only differentiate into bone, but also interact with the immune system to promote the healing process. We review in vitro and in vivo studies on the role of the immune system and bone marrow MSCs in bone healing and their interactions. A deeper understanding of this paradigm may provide clues to potential therapeu-tic targets in the healing process, thereby improving the reliability and safety of clinical applica-tions of MSCs to promote bone healing.

Purpose: We aimed to evaluate the impact of preconditioning adipose-derived mesenchymal stem cells (ADMSCs) with the autophagy inducer rapamycin (Rapa) on Cisplatin (Cis) induced ovarian toxicity in a rat model. Methods: ADMSCs were pretreated with 50 nmol/L rapa for two h in vitro. Another in vivo study included 96 female Sprague-Dawley rats divided into four equal groups: control, Cis, Cis +ADMSCs, and Cis +ADMSCs + Rapa. Rats were sacrificed after 2 and 6 weeks. Each group was subdivided into two equal subgroups: 6 rats were sacrificed to study ovarian parameters, and six were left for mating to evaluate the fertility index. Results: Autophagy activation was detected in ADMSCs + Rapa by increasing autophagosomes, high autophagy-specific LC3-II gene and protein expression, and low expression of p62 and mTOR genes. Moreover, transplantation of ADMSCs + Rapa restored balance between E2, FSH, and LH, increased antioxidant activity, and improved follicular count and quality after 2 and 6 weeks of treatment. Fertility index analysis manifested restoring reproductive capacity in the ADMSCs+ Rapa group at both intervals. Conclusions: Autophagy induction could enhance the therapeutic capability of ADMSCs by deactivating the mTOR pathway, which in turn promotes the ovarian folliculogenesis process after exposure to Cis.

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibro-blast-like cells which play important roles in tissue repair, inflammation, and immune modula-tion. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in the last years as key regulator of tumor microenvironment. Indeed, they are now con-sidered as active players in the pathophysiology of hematologic malignancies rather than passive by-standers in hematopoietic microenvironment. Once the malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progres-sion. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been showed that stromal cells themselves play a major role in several hematological malig-nancies’ pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterpart and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt the tumor/MSCs coupling. The present review will focus on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer pro-gression.

Background: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are no defined valid biomarkers for evaluating therapeutic outcomes of this disease. Numerous approaches have been made to meet this impact. Stem cells, one of these approaches, that might give various hopeful results that can be interpreted as a treatment for ALS This study aims to evaluate Mesenchymal Stem Cell (MSC) therapy as a promising novel treatment modality by estimating some parameters, such as immunological and biochemical factors. Methods: This study course involved 15 confirmed patients with ALS and was designed as an open-label, one-arm retrospective study to evaluate potential diagnostic biomarkers of repeated infusions of autologous bone marrow-derived mesenchymal stem cells (BM-MSC) administered at a dose of 1×106cells/kg BW with 1-month interval, in equal amounts in both intravenous (IV) and intrathecal (IT) simultaneously, by various biochemical and immunological parameters were evaluated during the three-month follow-up period. Results: Our study indicated that in the case of Immunological biomarkers ,Tumor Necrosis Factor-alpha (TNF-α) levels in the Cerebrospinal fluid (CSF) showed a significant decrease at month three after transplantation compared to levels at month zero, and the P-value was (P<0.01). No statistically significant changes were observed for other immunological and biochemical parameters and P-value (P>0.05). Conclusions: These results can indicate the benefit of stem cell transfusion in patients with ALS and suggest some diagnostic biomarkers. Several studies are required to approve these results.

Female infertility is a global medical condition that can be caused by various disorders of the reproductive system, including premature ovarian failure (POF), polycystic ovary syndrome (PCOS), endometriosis, Asherman syndrome, and preeclampsia. It affects the quality of life of both patients and couples. Mesenchymal stem cells (MSCs) have received increasing attention as a potential cell-based therapy with several advantages over other cell sources, including greater abundance, fewer ethical considerations, and high capacity for self-renewal and differentiation. Clinical researchers have examined the therapeutic use of MSCs in female infertility. In this review, we discuss recent studies on the use of MSCs in various reproductive disorders that lead to infertility. We also describe the role of microRNAs (miRNAs) and exosomal miRNAs in controlling MSC gene expression and driving MSC therapeutic outcomes. The clinical application of MSCs holds great promise for the treatment of infertility or ovarian insufficiency and to improve reproductive health for a significant number of women worldwide.

Osteoporosis is a bone condition where bones become weaker, leading to fractures, especially in older adults and postmenopausal women. Bioceramics for bone regeneration have indeed emerged as a promising solution for conditions like osteoporosis. Choosing the right bioceramic depends on how quickly it dissolves, how strong it is, and whether the body will react to it. Studies show that bioceramics can help bones grow back by activating (bone morphogenetic protein) BMP, (mitogen-activated protein kinase) MAPK, and Wingless/integrated (Wnt)/β-catenin pathways in the body when combined with stem cells, drugs, and supports. However, bioceramics have some problems like not being flexible enough and being prone to breaking, as well as difficulties in growing stem cells and finding the right supports for different bone types. While there has been progress in improving bioceramics for bone healing, we need to keep looking for new ideas from other areas of medicine to keep improving them. This review aims to add to the expanding field of scientific research by offering a detailed look at how bioceramics and growth factors contribute to bone regeneration. Ultimately, this knowledge will help in creating new types of bioceramics that can improve bone regrowth, providing new treatment options for people with bone diseases.

Many statistical distributions approximate well the frequent values of the maximum discharges, but have a very large spread for medium or rare probabilities of exceedance. This scattering defines a range of uncertainty of maximum discharges outside the measured values. Based on the upper (U) and lower (L) values of the uncertainty interval, a maximum discharge flood (MDF) and a maximum volume flood (MVF) are defined for each probability of exceedance. This approach is in agreement with the bivariate analysis, the contour lines for a certain probability of exceedance putting into evidence an infinity of couples (maximum discharge, flood volume). If the most critical combinations are selected, the MDF and MVF are derived. Apart from maximum discharge and flood volume, the shape of the design flood, characterized by the time to peak and the total duration, is also important. The easiest way to obtain the design flood is to use an analytical curve that passes through the characteristic points of the flood. Another possibility, which was largely developed in this paper, is to normalize the floods, then to define clusters of floods with similar shapes, and to obtain an average dimensionless flood for each class. Finally, a family of design floods with different shapes, but characterized by the same parameters for each probability of exceedance, are derived. The use of these floods in the design or operation of hydrotechnical works or in the delineation of flooded areas is presented at the end.

Mesenchymal Stem Cells derived from bone marrow (hBM-MSCs) are utilized in tendon tissue‐engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSC), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to hGDF-5 we supplemented each at doses of 1, 10, and 100 ng/mL and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated expression of Collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed upregulation of SCX-A (1.7-fold) at day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX (3.8-fold) and TNC (2.3-fold) after 3 days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this we explored expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines upregulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold) but a greater up-regulation of IL-10 (2.5-fold). Collagen type I and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification (fibroblast-like) with a Lenght/Width ratio increase at value higher than 1, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue engineering protocols.

Chronic rhinosinusitis is a common inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion and hyposmia. The genetic predisposition or the exposure to irritants can sustain the inflammatory response and the development of nasal polyposis. Nasal polyps are benign and teardrop-shaped growths that project in the nasal cavities and originate from the ethmoid sinuses. This inflammatory process is associated with high expression of IL-5 cytokine and infiltration of eosinophils. Humanized monoclonal antibodies targeting IL-5 or its receptor, represent a therapeutic strategy in the treatment of nasal polyposis in combination with corticosteroids. The molecular pathogenesis of nasal polyps in CRS patients is associated to the epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their typical phenotype acquiring a mesenchymal phenotype. TGFβ/SMAD, ERK, and Wnt/β-catenin pathways are altered in EMT during the nasal tissue remodeling. miRNA and inhibitor molecules targeting these altered signaling pathways are able to interfere with EMT; which could lead to alternative therapies. Nasal polyps are an alternative source of mesenchymal stem cells which can be easily isolated from surgical biopsies. A molecular understanding of the biology of PO-MSCs will contribute to delineating inflammatory process underlying the development of nasal polyps.

Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as therapeutic sources in several degenerative diseases. Recently, microRNAs (miRNAs) were mediated one of the therapeutic mechanisms of PD-MSCs in regenerative medicine. To enhance the therapeutic effects of PD-MSCs, we established functionally enhanced PD-MSCs with phosphatase of regenerating liver-1 overexpression (PRL-1(+)). However, the profile and functions of miRNAs induced by PRL-1(+) PD-MSCs in a rat model with hepatic failure prepared by bile duct ligation (BDL) remained unclear. Hence, the objectives of the present study were to analyze the expression of miRNAs and investigate their therapeutic mechanisms for hepatic regeneration via PRL-1(+) in a rat model with BDL. We selected candidate miRNAs based on microarray analysis. Under hypoxic conditions, compared with invaded naïve PD-MSCs, invaded PRL-1(+) PD-MSCs showed improved integrin-dependent migration ability through RHO family-targeted miRNA expression (e.g., hsa-miR-30a-5p, 340-5p, and 146a-3p). Moreover, rno-miR-30a-5p and 340-5p regulated engraftment into injured rat liver by transplanted PRL-1(+) PD-MSCs through the integrin family. Additionally, an increase in PDGFRA by suppressing rno-miR-27a-3p improved vascular structure in rat liver tissues after PRL-1(+) PD-MSCs transplantation. Furthermore, decreased rno-miR-122-5p was significantly correlated with increased proliferation of hepatocytes in liver tissues by PRL-1(+) PD-MSCs by activating IL-6 signaling pathway through the repression of rno-miR-21-5p. Taken together, these findings improve the understanding of therapeutic mechanisms based on miRNA-mediated stem cell therapy in liver diseases.

A recent study published in Nature Medicine (Mautner et al., Nat Med 2023 Nov 2. doi: 10.1038/s41591-023-02632-w. Epub ahead of print) reported findings regarding a four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients, aimed at comparing the therapeutic effectiveness of orthobiologic interventions against corticosteroid injections for the treatment of knee osteoarthritis (OA). The study concluded that, one-year post-treatment, all orthobiologic therapies examined were equivalent in effectiveness to each other and to corticosteroid injections. While we commend the scope and methodological rigor of the trial, the publication could be enhanced by a more comprehensive presentation of data to support the conclusions drawn. Particularly, the omission of baseline data for primary outcomes, the missing context to evaluate absolute values, the lack of discussion regarding interindividual variability, and the unexpectedly favorable results for corticosteroids that contrast the established literature, are areas that merit additional examination and insight. Here we aim to highlight these points for consideration, and advocate for the release of supplementary data to facilitate a comprehensive understanding and utilization of this rich dataset.

Infertility” is a condition defined by the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse or due to an impairment of a person’s capacity to reproduce either as an individual or with his/her partner’. The authors have set out to succinctly investigate, explore and assess infertility treatments harnessing the potential of stem cells to effectively and safely treat infertility, in addition to the legal and regulatory complexities at the heart of stem cell research, with an overview of the legislative state of affairs in six major European countries. In couples who cannot benefit from assisted reproductive technologies (ART) to treat their infertility, stem cells-based approaches have been shown to be a highly promising approach. Nonetheless, lingering ethical and immunological uncertainties require more conclusive findings and data before such treatment avenues can become mainstream and applied large scale. The isolation of human embryonic stem cells (ESCs) is ethically controversial, since their collection involves the destruction of human embryonic tissue. Overall, stem cell research has resulted in important new breakthroughs in the treatment of infertility. The effort to untangle the complex web of ethical and legal issues associated with such therapeutic approaches will have to rely on evidence-based, broadly shared standards, guidelines and best practices to make sure that the procreative rights of patients can be effectively reconciled with the core values at the heart of medical ethics.