Knee osteoarthritis (OA) is a leading cause of pain and disability. Although conventional treatments show modest benefits, pilot and phase I/II trials with bone marrow (BM) and adipose‐derived (AD) mesenchymal stromal cells (MSCs) point to the feasibility, safety, and occurrence of clinical and structural improvement in focal or diffuse disease. This study aimed to assess the safety and efficacy of the intra‐articular injection of single or repeated umbilical cord‐derived (UC) MSCs in knee OA. UC‐MSCs were cultured in an International Organization for Standardization 9001:2015 certified Good Manufacturing Practice‐type Laboratory. Patients with symptomatic knee OA were randomized to receive hyaluronic acid at baseline and 6 months (HA, n = 8), single‐dose (20 × 10⁶) UC‐MSC at baseline (MSC‐1, n = 9), or repeated UC‐MSC doses at baseline and 6 months (20 × 10⁶ × 2; MSC‐2, n = 9). Clinical scores and magnetic resonance images (MRIs) were assessed throughout the 12 months follow‐up. No severe adverse events were reported. Only MSC‐treated patients experienced significant pain and function improvements from baseline (p = .001). At 12 months, Western Ontario and Mc Master Universities Arthritis Index (WOMAC‐A; pain subscale) reached significantly lower levels of pain in the MSC‐2‐treated group (1.1 ± 1.3) as compared with the HA group (4.3 ± 3.5; p = .04). Pain Visual Analog scale was significantly lower in the MSC‐2 group versus the HA group (2.4 ± 2.1 vs. 22.1 ± 9.8, p = .03) at 12 months. For total WOMAC, MSC‐2 had lower scores than HA at 12 months (4.2 ± 3.9 vs. 15.2 ± 11, p = .05). No differences in MRI scores were detected. In a phase I/II trial (NCT02580695), repeated UC‐MSC treatment is safe and superior to active comparator in knee OA at 1‐year follow‐up. Stem Cells Translational Medicine 2018

A randomized controlled phase I/II clinical trial was designed to evaluate the safety and efficacy of encapsulated human umbilical cord mesenchymal stem cells in a plasma-derived biomaterial for regenerative endodontic procedures (REPs) in mature permanent teeth with apical lesions. The trial included 36 patients with mature incisors, canines, or mandibular premolars showing pulp necrosis and apical periodontitis. Patients were randomly and equally allocated between experimental (REP) or conventional root canal treatment (ENDO) groups. On the first visit, cavity access and mechanical preparation of the root canal were performed. Calcium hydroxide medication was used, and the cavity was sealed. Three weeks later, patients were treated following their assigned protocol of ENDO or REP. Clinical follow-up examinations were performed at 6 and 12 mo. Categorical variables were evaluated by Fisher’s exact test. Quantitative variables were compared using the Mann-Whitney test. The evolution over time of the percentage of perfusion units and the dimensions of lesion and cortical compromise were explored. After the 12-mo follow-up, no adverse events were reported, and the patients showed 100% clinical efficacy in both groups. Interestingly, in the REP group, the perfusion unit percentage measured by laser Doppler flowmetry revealed an increase from 60.6% to 78.1% between baseline and 12-mo follow-up. Sensitivity tests revealed an increase of the positive pulp response in the REP group at 12-mo follow-up (from 6% to 56% on the cold test, from 0% to 28% on the hot test, and from 17% to 50% on the electrical test). We present the first clinical safety and efficacy evidence of the endodontic use of allogenic umbilical cord mesenchymal stem cells encapsulated in a plasma-derived biomaterial. The innovative approach, based on biological principles that promote dentin-pulp regeneration, presents a promising alternative for the treatment of periapical pathology (ClinicalTrials.gov NCT03102879).

Global regional variations in dyslipidemia prevalence underscore the need for an updated global overview of the magnitude of dyslipidemia over time. To estimate the global prevalence of dyslipidemia in adults, considering scientific evidence published in the last 20 years, while analyzing associated sociodemographic and geographic factors. A systematic review and meta-analysis were conducted following PRISMA guidelines. The bibliographic search was performed in PubMed, SCOPUS, Web of Science, and EMBASE, including observational studies published between 2000 and 2025 that reported the prevalence of dyslipidemia components in general adult populations, including hypertriglyceridemia, hypercholesterolemia, hypoalphalipoproteinemia or low high-density lipoprotein cholesterol (HDL-C) levels (< 40 mg/dL for men and < 50 mg/dL for women), and elevated low-density lipoprotein cholesterol (LDL-C). Statistical analyses included meta-analysis with random effects models, stratified analyses by sex and country, and meta-regression by publication year. A total of 206 studies were included, primarily cross-sectional (98.5%). The global prevalence was 28.8% for hypertriglyceridemia, 24.1% for hypercholesterolemia, 38.4% for low HDL-C, and 18.93% for high LDL-C. Men presented a higher prevalence of hypertriglyceridemia (33.8% vs. 24.5% in women), while women showed a higher frequency of low HDL-C (40.5% vs. 34.1% in men). The highest prevalences of low HDL-C and mixed dyslipidemia patterns were observed in the Middle East and Latin America. Temporal trends revealed a progressive increase in hypertriglyceridemia and low HDL-C, with a decrease in hypercholesterolemia and high LDL-C. There is an epidemiological transition in the dyslipidemia profile, from classic hypercholesterolemia toward a predominance of hypertriglyceridemia and low HDL-C, with important differences by sex and region. These findings significantly affect cardiovascular prevention and health policies addressing residual risk beyond LDL-C control.

Nitric oxide (NO) is an intracellular messenger in several cell systems, but its contribution to embryonic stem cell (ESC) biology has not been characterized. Exposure of ESCs to low concentrations (2–20 μM) of the NO donor diethylenetriamine NO adduct confers protection from apoptosis elicited by leukaemia inhibitory factor (LIF) withdrawal. NO blocked caspase 3 activation, PARP degradation, downregulation of the pro-apoptotic genes Casp7, Casp9, Bax and Bak1 and upregulation of the anti-apoptotic genes Bcl-2 111, Bcl-2 and Birc6. These effects were also observed in cells overexpressing eNOS. Exposure of LIF-deprived mESCs to low NO prevented the loss of expression of self-renewal genes (Oct4, Nanog and Sox2) and the SSEA marker. Moreover, NO blocked the differentiation process promoted by the absence of LIF and bFGF in mouse and human ESCs. NO treatment decreased the expression of differentiation markers, such as Brachyury, Gata6 and Gata4. Constitutive overexpression of eNOS in cells exposed to LIF deprivation maintained the expression of self-renewal markers, whereas the differentiation genes were repressed. These effects were reversed by addition of the NOS inhibitor L-NMMA. Altogether, the data suggest that low NO has a role in the regulation of ESC differentiation by delaying the entry into differentiation, arresting the loss of self-renewal markers and promoting cell survival by inhibiting apoptosis.

Background/Objectives: Oreganum vulgare essential oil (OEO) is safe, effective, multifunctional, and widely used. This study aimed to evaluate OEO’s chemical composition and antimicrobial activity in vitro against S. aureus and E. coli. Methods: The composition of OEO was determined by gas chromatography–mass spectrometry (GC-MS). Results: Compounds included monoterpenes with known antimicrobial activity, such as 2-menthen-1-ol (36.33%), linalyl acetate (9.26%), terpinene-4-ol (9.01%), 4-thujanol (6.33%), menthen (5.81%), sabinene (5.18%), and carvacrol methyl ether (5.14%). Conclusions: OEO had a strong antimicrobial activity with a minimum inhibitory concentration (MIC) of 1.90 mg/mL for S. aureus and 0.49 mg/mL for E. coli after 18 h incubation. The minimum bactericidal concentration (MBC) was 7.9 mg/mL against S. aureus and 0.99 mg/mL against E. coli. Thus, OEO could be used as a natural antimicrobial against S. aureus and E. coli infections.

Various types of wounds represent a persistent healthcare burden that demands innovative and effective therapeutic solutions. Innovative approaches have emerged that focus on skin regeneration with minimal side effects. One such method is cell-free therapy that utilizes the secretome of human mesenchymal stem cells (hMSCs) as a promising alternative to traditional cell-based therapies, leveraging a complex mixture of bioactive molecules, including growth factors, cytokines, and extracellular vesicles, to accelerate tissue regeneration. This systematic review synthesizes the findings of 35 studies evaluating the impact of hMSC-derived secretomes on wound healing, with a focus on their regenerative, immunomodulatory, and angiogenic effects. The influence of MSC sources (adipose tissue, bone marrow, umbilical cord) and culture conditions on secretome composition and efficacy in the cutaneous wound healing process is examined, highlighting their therapeutic potential in regenerative medicine. This review also explores emerging preclinical and clinical applications, highlighting promising results, such as enhanced fibroblast proliferation, reduced inflammation, and improved extracellular matrix remodeling. In addition, advances in secretome-based biomaterials, including hydrogels and scaffolds, which optimize therapeutic delivery and efficacy are discussed. Despite the growing body of evidence supporting the safety and efficacy of secretomes, challenges remain regarding standardization, large-scale production, and clinical validation. This review highlights the potential of MSC-derived secretomes as a next-generation cell-free approach for wound healing and regenerative medicine.