Umbilical Cord

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are recognized as a promising strategy for cell-free therapy, however, their therapeutic role in pulmonary fibrosis remains unrevealed. Here, we report the safety and efficacy of MSC-EVs from human umbilical cord (hUCMSC-EVs) evaluated in mouse models and pulmonary fibrosis patients. We established a rigorous system to produce high-quality of hUCMSC-EVs, characterized by miRNA, protein, and metabolite profiles. When administered via nebulization, hUCMSC-EVs predominantly accumulated in murine lungs and ameliorated bleomycin-induced pulmonary fibrosis, with increased survival rate (from 20% to 80%), restored lung volume, and attenuated injury severity accompanied by elevated oxyhemoglobin saturation and improved pulmonary function evaluations. We performed a phase l clinical trial involving twenty-four patients in a randomized, single-blind, and placebo-controlled study to treat pulmonary fibrosis (MR-46-22-004531, ChiCTR2300075466). All participants tolerated the nebulized hUCMSC-EVs well, with no serious adverse events. Patients receiving the combined therapy of nebulized hUCMSC-EVs and routine treatment demonstrated significant improvements in both lung function indices (forced vital capacity and maximal voluntary ventilation) and respiratory health status (as measured by the Saint George's Respiratory Questionnaire and Leicester Cough Questionnaire. Overall, patients upon the additional therapy with nebulized hUCMSC-EVs gained significant benefits compared with those accepted only routine treatment. Remarkably, two patients with advanced post-inflammatory pulmonary fibrosis exhibited clinically significant regression on serial CT scans after hUCMSC-EVs therapy. These findings suggest that nebulized hUCMSC-EVs could be used as a promising therapeutic strategy for treating pulmonary fibrosis diseases.

UVB radiation induces oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, compromised barrier function, and an increased risk of carcinogenesis. Addressing or preventing photoaging may offer a promising therapeutic avenue for these conditions. Recent research indicated that mesenchymal stem cells (MSCs) exhibit significant therapeutic potential for various skin diseases. Given that extracellular vesicles (EV) can deliver diverse cargo to recipient cells and elicit similar therapeutic effects, we investigated the roles and underlying mechanisms of both adipose-derived MSC-derived EV (AMSC-EV) and umbilical cord-derived MSC-derived EV (HUMSC-EV) in photoaging. Our findings indicated that in vivo, treatment with AMSC-EV and HUMSC-EV resulted in improvements in wrinkles and skin hydration while also mitigating skin inflammation and thickness alterations in both the epidermis and dermis. Additionally, in vitro studies using human keratinocytes (HaCaTs), human dermal fibroblast cells (HDFs), and T-Skin models revealed that AMSC-EV and HUMSC-EV attenuated senescence, reduced levels of reactive oxygen species (ROS) and DNA damage, and alleviated inflammation induced by UVB. Furthermore, EV treatment enhanced cell viability and migration capacity in the epidermis and promoted extracellular matrix (ECM) remodeling in the dermis in photoaged cell models. Mechanistically, proteomics results showed that TIMP1 was highly expressed in both AMSC-EV and HUMSC-EV and could exert similar effects as MSC-EV. In addition, we found that EV and TIMP1 could inhibit Notch1 and downstream targets Hes1, P16, P21, and P53. Collectively, our data suggests that both AMSC-EV and HUMSC-EV attenuate skin photoaging through TIMP1/Notch1.

BackgroundBackground: Exosomes (Exos) derived from mesenchymal stem cells (MSCs) share similar biological functions with MSCs but are more stable under various pathophysiological conditions, with a lower risk of immune rejection. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising source of MSC-derived exosomes (MSC-Exos), particularly for the treatment of osteoarthritis (OA), a degenerative joint disease characterized by inflammation and cartilage damage.MethodsIn this study, we conducted in vitro experiments on mouse articular chondrocytes and treated mouse OA models with hUC-MSCs-Exos. To validate the results of hUC-MSCs-Exos in humans, a randomized, double-blind, ascending dose study was conducted to investigate the safety and efficacy of hUC-MSCs-Exos in the treatment of OA, and human chondrocyte toxicity experiments were conducted prior to the clinical trial.ResultsIn this study, we successfully extracted hUC-MSCs and verified their multilineage differentiation ability in different culture media. We then verified the Exos morphology and the expression of CD9, CD63, TSG1, and CALN. In preclinical experiments in vitro and in vivo, we verified that hUC-MSC- Exos can reduce the inflammatory response of articular cartilage and promote its regeneration. Finally, clinical experiments confirmed that hUC-MSC- Exos injection treatment of OA patients did not cause any adverse consequences, and a certain degree of effectiveness was found in the comparison of clinical scores and MRI examinations before and after treatment.ConclusionsThis study shows that hUC-MSC-derived exosomes effectively reduce inflammation and promote cartilage regeneration in osteoarthritis, with demonstrated safety and efficacy in both preclinical and clinical settings.Trial registrationTrial No.MR-13-24-017929. Registered 11 February 2023, https://medicalresearch.org.cn/login# .

ImportanceThe Apgar score, the first clinical assessment to direct measures to stabilize newborn infants, is also used for risk assessment. Its accuracy in estimating outcomes remains poor among very preterm (VPT) infants.ObjectiveTo assess the utility of the combined 5-minute Apgar score and umbilical artery pH (UA-pH) for estimating risks of mortality and severe neonatal morbidity among VPT infants.Design, setting, and participantsThis cohort study (Effective Perinatal Intensive Care in Europe [EPICE]) analyzed infants born at less than 32 weeks' gestation between April 2011 and September 2012 across 11 European countries. All liveborn VPT infants with Apgar scores and UA-pH data were included. Data were analyzed between February and December 2025.ExposuresApgar score at 5 minutes and UA-pH. The Apgar score was classified as lower than 7 and 7 or higher, and the UA-pH values were categorized as low (Main outcomes and measuresCombined outcome of mortality and/or any adverse morbidity (intraventricular hemorrhage [IVH] >grade 2, cystic periventricular leukomalacia, moderate or severe bronchopulmonary dysplasia [BPD], retinopathy of prematurity ≥stage 2, and necrotizing enterocolitis). Modified Poisson regression was used to estimate relative risks (RRs) between the exposure and the combined mortality and morbidity outcome and 3 individual components: mortality, IVH, and BPD. Models were adjusted for perinatal variables associated with Apgar score and UA-pH and adverse neonatal outcomes.ResultsOf 7900 liveborn infants in the EPICE cohort, 4174 (52.8%) had information on Apgar score and UA-pH. These infants included 2249 males (53.9%) and had a median [IQR] gestational age of 29.9 [27.9-31.0] weeks and median [IQR] birth weight of 1240 [960-1520] g. A total of 367 infants (8.8%) had an Apgar score 7 or higher but a low UA-pH, 558 (13.4%) had an Apgar score lower than 7 but a normal UA-pH, and 196 (4.7%) had an Apgar score lower than 7 and a low UA-pH. Infants with an Apgar score lower than 7 had a higher frequency of the combined outcome among those with a normal UA-pH (270 [48.4%] vs 596 [19.5%]) and a low UA-pH (108 [55.1%] vs 596 [19.5%]), with similar adjusted RRs (ARRs; low: 1.4 [95% CI, 1.2-1.7]; normal: 1.4 [95% CI, 1.3-1.6]). For mortality risk, associations were robust for an Apgar score lower than 7 and a low UA-pH (ARR, 2.4; 95% CI, 1.7-3.3) and absent with an Apgar score of 7 or higher and a low UA-pH (ARR, 1.2; 95% CI, 0.8-1.8). IVH risk was increased in all 3 subcategories, including an Apgar score of 7 or higher with a low UA-pH (ARR, 2.0; 95% CI, 1.3-3.0). BPD risk was associated only with an Apgar score lower than 7 and a normal UA-pH (ARR, 1.4; 95% CI, 1.2-1.7).Conclusions and relevanceIn this cohort study of VPT infants, combining information on UA-pH with the 5-minute Apgar score was associated with improved accuracy in estimating the risk of some adverse outcomes-notably mortality and IVH, which occurred soon after birth. These results highlight the importance of exploring the associations of early markers of risk with neonatal mortality and key neonatal morbidities separately.