Extracellular vehicles (EVs) are efficient biomarkers of disease and participate in disease pathogenesis; however, their use as clinical therapies to modify disease outcomes remains to be determined. Cell-based immune therapies, including regulatory T cells (Tregs), are currently being clinically evaluated for their usefulness in suppressing pro-inflammatory processes. The present study demonstrates that ex vivo expanded Tregs generate a large pool of EVs that express Treg-associated markers and suppress pro-inflammatory responses in vitro and in vivo. Intravenous injection of Treg EVs into an LPS-induced mouse model of inflammation reduced peripheral pro-inflammatory transcripts and increased anti-inflammatory transcripts in myeloid cells as well as Tregs. Intranasal administration of enriched Treg EVs in this model also reduced pro-inflammatory transcripts and the associated neuroinflammatory responses. In a mouse model of amyotrophic lateral sclerosis, intranasal administration of enriched Treg EVs slowed disease progression, increased survival, and modulated inflammation within the diseased spinal cord. These findings support the therapeutic potential of expanded Treg EVs to suppress pro-inflammatory responses in human disease.

Background: Although there is strong evidence linking triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to insulin resistance and diabetes mellitus, its clinical importance in pregnant women has not been well determined. This study sought to determine the connection between the TG/HDL-C ratio in the first trimester and the eventual onset of gestational diabetes mellitus (GDM).Methods: We performed a secondary analysis of open-access data from a prospective cohort study. This present study included 590 singleton pregnant women at 10-14 weeks who visited the outpatient clinics for prenatal checks and were recorded at Incheon Seoul Women’s Hospital and Seoul Metropolitan Government Seoul National University Boramae Medical Center in Korea. A binary logistic regression model, a series of sensitivity analyses, and subgroup analysis were used to examine the relationship between TG/HDL-C ratio and incident GDM. A receiver operating characteristic (ROC) analysis was also conducted to assess the ability of the TG/HDL-C ratio to predict GDM.Results: The mean age of the included individuals was 32.06 ± 3.80 years old. The mean TG/HDL-C ratio was 1.96 ± 1.09. The incidence rate of GDM was 6.27%. After adjustment for potentially confounding variables, TG/HDL-C ratio was positively associated with incident GDM (OR=1.77, 95%CI: 1.32-2.38, P=0.0001). Sensitivity analyses and subgroup analysis demonstrated the validity of the relationship between the TG/HDL-C ratio and GDM. The TG/HDL-C ratio was a good predictor of GDM, with an area under the ROC curve of 0.7863 (95% CI: 0.7090-0.8637). The optimal TG/HDL-C ratio cut-off value for detecting GDM was 2.2684, with a sensitivity of 72.97% and specificity of 75.05%.Conclusion: Our results demonstrate that the elevated TG/HDL-C ratio is related to incident GDM. The TG/HDL-C ratio at 10-14 weeks could help identify pregnant women at risk for GDM and may make it possible for them to receive early and effective treatment to improve their prognosis.

Human umbilical cord‐derived mesenchymal stem/stromal cells (UMSCs) demonstrate great therapeutic potential in regenerative medicine. The use of UMSCs for clinical applications requires high quantity and good quality of cells usually by in vitro expansion. However, the heterogeneity and the characteristics of cultured UMSCs and the cognate human umbilical cord tissue at single‐cell resolution remain poorly defined. In this study, we created a single‐cell transcriptome profile of human umbilical cord tissue and the cognate culture‐expanded UMSCs. Based on the inferred characteristics of cell clusters and trajectory analysis, we identified three subgroups in culture‐expanded UMSCs and putative novel transcription factors (TFs) in regulating UMSC state transition. Further, putative ligand–receptor interaction analysis demonstrated that cellular interactions most frequently occurred in epithelial‐like cells with other cell groups in umbilical cord tissue. Moreover, we dissected the transcriptomic differences of in vitro and in vivo subgroups and inferred the telomere‐related molecules and pathways that might be activated in UMSCs for cell expansion in vitro. Our study provides a comprehensive and integrative study of the transcriptomics of human umbilical cord tissue and their cognate‐cultured counterparts, which paves the way for a deeper understanding of cellular heterogeneity and offers fundamental biological insight of UMSCs‐based cell therapy.