Porcine umbilical cord exosomes promote regenerative skin repair through miR-192-5p/DSC1-mediated angiogenesis and collagen matrix optimization.

Cellular aging is a complicated event known for gradually reducing homeostasis, leading to a higher susceptibility to diseases and mortality. Since the behavior of Hematopoietic Stem Cells (HSCs) is potentially affected by plasma-derived exosomes, this study aimed to investigate whether the plasma-derived exosome of young and elderly human donors can deliver "youth" or "aging" signals into human umbilical cord blood-derived HSCs in vitro. Exosomes were isolated from four young (Y-exo) and four old (O-exo) donors. Umbilical cord blood-derived HSCs were exposed to two concentrations of exosomes (5 and 10 μg/mL). Then, lineage differentiation (CD41 and CD38), the mRNA and protein expression of IL-1β and IL- 6, and NFκB activity were evaluated using flow cytometry, qRT-PCR Enzyme-Linked Immunosorbent Assay (ELISA) methods, and western blot techniques, respectively. The lineage-specific markers CD41 and CD38 expression were increased after exposure to O-exo compared to Y-exo at the concentration of 10 μg/mL (P<0.001). The HSCs treated with 10 μg/mL O-exo increased protein and mRNA expression of IL-1β and IL-6 compared to Y-exo at 10 μg/mL concentration (P<0.01). Furthermore, a significant difference was seen in p-NF-κB levels between O-exo and Y-exo at the concentration of 10 μg/mL (P=0.0014). Our findings advocated the concept that circulating exosomes of old and young individuals may differently affect the pathways involved in the aging process in HSCs.Therefore, exosomes may be applied as therapeutic agents for regenerative medicine.

Altered umbilical cord blood complement profiles in preeclampsia and preterm birth pregnancies.

Culturing Potential: advances in ex vivo cell culture systems for haematopoietic cell-based regenerative therapies.

Human umbilical cord blood cells-secreted exosomal MFG-E8 regulates microglia polarization and ameliorates hypoxic-ischemic brain damage in neonatal rats by SOCS3/STAT3 axis.

Per- and polyfluoroalkyl substances and the gut microbiota in infants: A scoping review.

Erratum to “A workflow to study the microbiota profile of piglet’s umbilical cord blood: from sampling to data analysis” [Animal Open Space 2 (2023) 100031

ARID1A gene variants and fetal hydrocephalus: First evidence of mRNA decay escape.

Physiological-based cord clamping (PBCC) involves aeration of the newborn lung before umbilical cord clamping. As the infant can continue to receive oxygen from the mother during PBCC, the dynamics of transplacental oxygen transfer are unknown, particularly following the onset of pulmonary gas exchange. We have investigated the effects of pulmonary ventilation with supplemental oxygen during PBCC on transplacental oxygen transfer in preterm lambs. Pregnant ewes and their fetuses (n = 8; 127 days of gestation; term 147 days) were instrumented with catheters and flow probes under general anesthesia to measure oxygen transfer across the placenta. Before umbilical cord clamping, lambs were intubated and mechanically ventilated with a fraction of inspired oxygen ([Formula: see text]) that increased every 10 min, from 0.21 to 0.5 and then 1.0. Data were analyzed using a mixed-effects analysis with a Holm-Šídák post hoc test. During PBCC, ventilation of lambs significantly decreased oxygen uptake across the placenta from 317.7 ± 15.0 to 166.5 ± 26.9 (P = 0.0028) and to 73.6 ± 34.3 mL/min/kg (P = 0.0009) at [Formula: see text] levels of 0.21 and 0.5, respectively. Ventilation with a [Formula: see text] of 1.0 reversed oxygen uptake across the placenta (-37.2 ± 14.0 mL/min/kg; P < 0.0001), resulting in oxygen transfer from lamb to ewe. In contrast, oxygen delivery to the lamb, via the umbilical vein, remained unchanged with increasing [Formula: see text] (P = 0.4485). During PBCC, pulmonary oxygen uptake by the newborn reduces oxygen uptake across the placenta, and when oxygen levels are in excess, the mother acts as an "oxygen sink," reducing the risk of hyperoxemia of the newborn.NEW & NOTEWORTHY This study investigated transplacental oxygen transfer during physiological-based cord clamping in preterm lambs. During physiological-based cord clamping, ventilating newborn lambs reduced oxygen uptake across the placenta and that ventilation with high oxygen (1.0 [Formula: see text]) reversed the oxygen gradient, resulting in newborn to mother oxygen transfer. Our findings indicate that the mother can act as an "oxygen sink" that protects the newborn from excess oxygen during physiological-based cord clamping.

Effects of combined oral contraceptives on steroids and lipidomics in newborns of mothers with polycystic ovary syndrome.

Altered immune cell profiles in maternal and umbilical cord blood and fetal growth restriction: A flow cytometric analysis.

The umbilical cord blood exosome MFG-E8 alleviates hypoxic-ischemic encephalopathy brain injury in neonatal rats by restoring autophagy flux and inhibiting ferroptosis through GSK3β/β-catenin signaling.

Graft-Versus-Host disease (GVHD) is a leading contributor to morbidity and mortality following stem cell transplantation (SCT). Current GVHD prevention methods utilize a combination of immunosuppressive drugs to prevent injury to host tissues. Post-Transplant cyclophosphamide (PTCy) for GVHD prophylaxis initially was shown to be effective in the adult haploidentical SCT setting and later in matched donor SCTs. Implementation of PTCy has increased the utilization of alternative donors in curative SCT. In pediatrics, PTCy for GVHD prophylaxis has recently demonstrated safety and efficacy. However, its widespread use still lags compared with adult use due to variability between institutions and the lack of prospective pediatric trials. In this review, we summarize the pathophysiology of GVHD and PTCy and synthesize studies in adults and children of PTCy for GVHD prophylaxis, which support its use. We focus on using PTCy in haploidentical, matched donor, and umbilical cord blood transplantation settings, and discuss the current and future role of PTCy in pediatrics. Our goal is to inform pediatric SCT physicians regarding the use of PTCy to help reduce morbidity and mortality following transplantation.

PFGA12 ameliorates Hypoxic-Ischemic brain injury by directly regulating PRDX1 and inhibiting ferroptosis.

IntroductionMesenchymal stem cell-derived exosomes have garnered considerable attention in regenerative medicine due to their non-immunogenicity, low infusion toxicity, easy accessibility, straightforward preservation, and minimal ethical concerns. While ultracentrifugation is the prevailing method for high-purity exosome isolation, it is limited by low throughput and the need for specialized infrastructure. This study investigates tangential flow filtration (TFF) as a promising alternative for exosome isolation. This technique offers simpler operation, higher yields, and improved recovery rates compared to ultracentrifugation.MethodsHuman umbilical cord mesenchymal stem cells (hUCMSCs) were cultured in a 3D microcarrier-bioreactor system, and exosomes were extracted from the conditioned medium using either ultracentrifugation or an automated and enclosed TFF system. Subsequently, we compared the quantity, quality and therapeutic efficacy of the exosomes isolated via both approaches, evaluating their effects in vitro and in a mouse model of diabetic wound healing.ResultsOur findings demonstrate that the TFF method effectively isolates high-quality exosomes that meet the standards set by the Minimum Information for Studies of Extracellular Vesicles (MISEV) 2023 guidelines, while achieving a significantly higher extraction yield compared to the traditional ultracentrifugation. Furthermore, both TFF and ultracentrifugation-derived exosomes demonstrate comparable biological activity in vitro and similar therapeutic potential for treating diabetic wound healing, potentially through promoting M2 macrophage polarization and angiogenesis.ConclusionThe results indicate that TFF is a viable method for scalable and efficient exosome production, facilitating advancements in clinical applications for diabetic wound repair.

Omphalitis, a bacterial infection of the umbilical stump and surrounding periumbilical tissues, represents a significant cause of preventable neonatal morbidity and mortality, particularly in resource-limited settings. While its incidence is low in high-income countries due to standardized hygienic practices, it remains a formidable clinical challenge in vulnerable populations globally. This infection typically presents within the first two weeks of life, with a spectrum ranging from mild cellulitis to a life-threatening systemic illness. The pathophysiology involves bacterial invasion through the necrotic cord stump, with the unique patency of the umbilical vessels facilitating rapid progression to severe complications such as necrotizing fasciitis, umbilical vein thrombophlebitis, portal vein thrombosis, and sepsis. The bacteriology is often polymicrobial, predominantly featuring Staphylococcus aureus (including MRSA), Streptococcus pyogenes, and Gram-negative organisms like Escherichia coli and Klebsiella pneumoniae. Risk factors are multifactorial, including low birth weight, unhygienic cord care practices, and application of harmful traditional substances. Diagnosis is primarily clinical, supported by laboratory investigations (inflammatory markers, blood cultures) and imaging, notably ultrasonography, to detect deep tissue involvement. Management necessitates a prompt, aggressive approach with broad-spectrum intravenous antibiotics, with surgical intervention required for complications like abscess formation or necrotizing fasciitis. Crucially, prevention is the cornerstone of reducing the disease burden, with "dry cord care" recommended in hygienic settings and topical application of chlorhexidine to the umbilical stump proven to significantly reduce incidence and mortality in high-risk environments. This comprehensive review synthesizes current evidence on the etiology, pathogenesis, clinical presentation, management, and preventative strategies for omphalitis, highlighting the critical intersection of clinical vigilance and public health intervention.

Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by insulin resistance and pancreatic β-cell dysfunction. While human umbilical cord mesenchymal stem cells (HUCMSCs) show therapeutic potential, their efficacy can be limited by the harsh in vivo microenvironment. 20(R)-Rg3, a ginsenoside with anti-inflammatory and antioxidant properties, may enhance HUCMSCs’ function, but the combined effect and mechanism of this “cell-molecule” strategy remain unclear. This study aimed to investigate the therapeutic effects and underlying mechanisms of a combination therapy using 20(R)-Rg3 and HUCMSCs in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mouse model. Diabetic mice were treated with PBS, HUCMSCs alone, or HUCMSCs pre-treated with 20(R)-Rg3. Fasting blood glucose and body weight were monitored. Insulin resistance was assessed via oral glucose tolerance tests (OGTTs) and intraperitoneal insulin tolerance tests (IPITTs). Serum biochemical parameters (lipids, liver and kidney function, insulin, C-peptide) were analyzed. Histopathological examination (H&amp;E, PAS) of the liver, kidney, and pancreas was performed, alongside immunofluorescence for islet hormones. Transcriptomic analysis (RNA-seq) was conducted on HUCMSCs with or without 20(R)-Rg3 pretreatment to elucidate potential signaling pathways. Results demonstrated that the combination significantly reduced hyperglycemia and improved insulin sensitivity more effectively than HUCMSCs alone. It also ameliorated dyslipidemia, enhanced liver and kidney function, promoted glycogen synthesis, and facilitated pancreatic islet “regeneration”. Transcriptomic analysis indicated that the synergistic effect is primarily mediated through activation of the PI3K/Akt signaling pathway. These findings suggest that 20(R)-Rg3 potentiates the therapeutic efficacy of HUCMSCs, providing a promising combinatorial strategy for T2DM treatment.

Objective We aimed to investigate the impact of delayed cord clamping (DCC) on the levels of blood mesenchymal (MSCs), hemopoietic progenitor (HPCs), and immune cells in very preterm neonates. Methods We prospectively examined 21 neonates with a median gestational age of 32 weeks (interquartile range, IQR 29–32) who had DCC, and 19 neonates with a median gestational age of 31 weeks (IQR 30–32) who had immediate cord clamping (ICC). We measured the levels of MSCs, HPCs, very small embryonic-like stem cells (VSELs), early endothelial progenitor cells (EPCs), late EPCs, and the immunophenotype in the first, 10th, and 30th day of life, and associated them with late-onset sepsis and bronchopulmonary dysplasia (BPD). Results DCC-neonates compared to ICC-neonates had significantly higher values of MSCs (846 vs. 316 cells per million cytometric events, p = 0.003), HPCs (191 vs. 115 cells per million cytometric events, p = 0.034), and lower values of VSELs (21 vs. 37 cells per million cytometric events, p = 0.044) and late EPCs (7 vs. 19 cells per million cytometric events, p = 0.017) at birth. Neonates with late-onset sepsis, in comparison to neonates with no sepsis, had significantly higher values of early (20 vs. 0.3 cells per million cytometric events, p = 0.011) and late EPCs (32 vs. 8 cells per million cytometric events, p = 0.033). In addition, neonates with BPD had significantly higher values of late EPCs compared to neonates without BPD (27 vs. 8 cells per million cytometric events, p = 0.041). DCC, adjusted for gestational age and birth weight, was significantly associated with higher levels of MSCs, HPCs, and lower levels of VSELs and late EPCs. Conclusions In very preterm neonates with DCC, MSCs and HPCs are higher, while VSELs and late EPCs are lower in the umbilical cord blood, compared to neonates with ICC. Early and late EPCs were associated with late-onset sepsis and BPD. Further studies are warranted to explore the association of these findings with the long-term clinical outcomes.

This study aimed to determine the most feasible perinatal tissue for Good Manufacturing Practice (GMP)-compliant banking of mesenchymal stromal-like cells (MSC-like cells). It was hypothesized that amniotic fluid collected during cesarean section would yield lower contamination rates and greater processing feasibility compared with other perinatal tissues. This prospective observational study was conducted at a tertiary university hospital and included 32 healthy term pregnancies. A total of 160 perinatal samples-amniotic fluid, amniotic membrane, umbilical cord, intact placenta, and placental fragments-were obtained. A validated feasibility scoring system evaluated material acquisition difficulty, transportation logistics, storage duration, and processing complexity. Samples were stratified by delivery mode (cesarean section vs. vaginal delivery) and collection timing (within vs. outside laboratory working hours). Stem cell isolation, sterility assessment, and immunophenotypic characterization were performed. Due to the absence of trilineage differentiation assays and maternal-fetal origin confirmation, the isolated cells were defined as MSC-like cells rather than definitive fetal MSCs. Statistical analyses were performed using chi-square and Mann-Whitney U tests (p < 0.05). Samples collected via cesarean section demonstrated significantly lower rates of blood contamination (25.8% vs. 60.0%, p < 0.001) and bacterial contamination (25.8% vs. 60.0%, p < 0.001) compared with those from vaginal deliveries. Amniotic fluid achieved the highest acquisition score, required no enzymatic digestion, and had the shortest median isolation time (45min). It exhibited the lowest overall contamination and was the most suitable source for GMP-oriented MSC-like cell processing. Conversely, intact placenta and placental fragments showed the highest contamination rates, longest enzymatic processing times, and greatest logistical burden. While collection timing affected storage duration and workflow continuity, tissue type and delivery mode were the dominant determinants of feasibility. Cesarean section-derived amniotic fluid appears to be the most practical, sterile, and processing-efficient perinatal source for GMP-adapted MSC-like cell banking within the evaluated parameters. These results support its prioritization in the development of standardized collection and processing protocols for perinatal stromal cell applications in regenerative medicine.

Background: Vitamin B₁₂ is an essential micronutrient that plays a critical role in DNA synthesis, methylation, and cellular energy metabolism. Its deficiency during the intrauterine period has been associated with increased oxidative stress and DNA damage, which may have lasting effects on the newborn. 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative DNA damage, is widely used to evaluate these processes. However, the effects of vitamin B₁₂ deficiency on such biomarkers at birth remain insufficiently investigated. Methods: This single-center, prospective case-control study included 48 term newborns with vitamin B₁₂ deficiency and 40 healthy controls matched for gestational age. Vitamin B₁₂, total oxidant status, total antioxidant status, oxidative stress index, and 8-hydroxy-2'-deoxyguanosine were measured from umbilical cord venous blood obtained immediately after delivery. Oxidant and antioxidant levels were determined using colorimetric methods, and oxidative DNA damage was assessed by enzyme-linked immunosorbent assay. Group comparisons were made using appropriate statistical tests, with significance set at p&lt;0.05. Results: Vitamin B₁₂ levels were significantly lower in the patient group. Levels of 8-hydroxy-2'-deoxyguanosine, total oxidant status, and oxidative stress index were significantly higher, whereas total antioxidant status showed no significant difference between groups. Conclusions: Term newborns with vitamin B₁₂ deficiency exhibited increased oxidative stress and measurable oxidative DNA damage at birth. The unchanged total antioxidant status may reflect the immature antioxidant defense system in the neonatal period. Biomarker evaluation at delivery could assist in early identification and intervention for infants at risk of complications associated with intrauterine vitamin B₁₂ deficiency.