Reconstitution of human microglia and resident T cells in the brain of humanized DRAGA mice.

Humanized mouse models are valuable tools for investigating the human immune system in response to infection and injury. We have previously described the human immune system (HIS)-DRAGA mice (HLA-A2.HLA-DR4.Rag1KO.IL-2RgKO.NOD) generated by infusion of Human Leukocyte Antigen (HLA)-matched, human hematopoietic stem cells from umbilical cord blood. By reconstituting human cells, the HIS-DRAGA mouse model has been utilized as a "surrogate in vivo human model" for infectious diseases such as Human Immunodeficiency Virus (HIV), Influenza, Coronavirus Disease 2019 (COVID-19), scrub typhus, and malaria. This humanized mouse model bypasses ethical concerns about the use of fetal tissues for the humanization of laboratory animals. Here in, we demonstrate the presence of human microglia and T cells in the brain of HIS-DRAGA mice. Microglia are brain-resident macrophages that play pivotal roles against pathogens and cerebral damage, whereas the brain-resident T cells provide surveillance and defense against infections. Our findings suggest that the HIS-DRAGA mouse model offers unique advantages for studying the functions of human microglia and T cells in the brain during infections, degenerative disorders, tumors, and trauma, as well as for testing therapeutics in these pathological conditions.

Perioperative complications of middle cerebral artery occlusion in rats alleviated by human umbilical cord mesenchymal stem cells.

For acute ischemic stroke treatment, the limitations of treatment methods and the high incidence of perioperative complications seriously affect the survival rate and postoperative recovery of patients. Human umbilical cord mesenchymal stem cells (hucMSCs) have multi-directional differentiation potential and immune regulation function, which is a potential cell therapy. The present investigation involved developing a model of cerebral ischemia-reperfusion injury by thrombectomy after middle cerebral artery occlusion (MCAO) for 90 min in rats and utilizing comprehensive multi-system evaluation methods, including the detection of brain tissue ischemia, postoperative survival rate, neurological score, anesthesia recovery monitoring, pain evaluation, stress response, and postoperative pulmonary complications, to elucidate the curative effect of tail vein injection of hucMSCs on MCAO's perioperative complications. Based on our research, it has been determined that hucMSCs treatment can reduce the volume of brain tissue ischemia, promote the recovery of neurological function, and improve the postoperative survival rate of MCAO in rats. At the same time, hucMSCs treatment can prolong the time of anesthesia recovery, relieve the occurrence of delirium during anesthesia recovery, and also have a good control effect on postoperative weight loss, facial pain expression, and lung injury. It can also reduce postoperative stress response by regulating blood glucose and serum levels of stress-related proteins including TNF-α, IL-6, CRP, NE, cortisol, ß-endorphin, and IL-10, and ultimately promote the recovery of MCAO's perioperative complications.

The side-entry method: An easy approach of umbilical vascular catheterization.

Umbilical vascular catheterization remains an important technique in case a newly born infant requires resuscitation. Most textbooks recommend a complete transection of the umbilical cord and subsequent opening of vessel lumen with an iris forceps to place the catheter. That method, however, is challenging in emergencies. Here we present an easy, quick and safe method of placing the umbilical catheters. The side-entry method could be an alternative to the conventional approach and is worth to enter pediatric textbooks and neonatal resuscitation guidelines.

An Assessment of the Relationships Between Umbilical Cord Blood Gas Analysis, APGAR (Appearance, Pulse, Grimace, Activity, and Respiration) Scores, and Neonatal Outcomes.

Introduction Intrapartum hypoxic-ischemic injury is a condition that significantly affects neonatal health and, therefore, needs to be attended to urgently. Umbilical cord blood gas analysis (BGA) results and APGAR (appearance, pulse, grimace, activity, and respiration) scores are commonly used to assess birth asphyxia and the severity of neonatal acidemia. In this context, this study was conducted to investigate the correlations of BGA results and APGAR scores with neonatal outcomes to determine the combined value of BGA results and APGAR scores in neonatal health assessment. Methods The sample of this retrospective cohort study consisted of 593 consecutive-term newborns delivered in a tertiary referral center in Turkey between January 2020 and December 2022. All newborns' maternal, delivery, and neonatal characteristics, BGA results, and APGAR scores were analyzed to determine correlations with composite adverse neonatal outcomes. The study's primary outcome was defined as the rate of the composite adverse neonatal outcomes, whereas the secondary outcomes were determined as the impact of maternal and neonatal characteristics on composite neonatal morbidity and the correlation between the one- and five-minute APGAR scores and umbilical cord BGA parameters. Results Of the 593 infants included in the study, 191 (32.2%) infants experienced composite adverse neonatal outcomes, primarily mechanical ventilation (47.7%), followed by respiratory distress/syndrome (35.6%). Significant correlations were detected between composite adverse neonatal outcomes and advanced maternal age (p = 0.025), cesarean section history (p < 0.001), preterm delivery (p < 0.001), lower one- and five-minute APGAR scores (p < 0.001 for both cases), and acidemia severity (p = 0.007). However, the correlations between BGA parameters and APGAR scores were weak (r < 0.2). Conclusion This study investigated the correlations between neonatal mortality and morbidity and maternal factors, delivery characteristics, and fetal features, including one- and five-minute APGAR scores and BGA parameters. Nevertheless, weak correlations between BGA parameters and APGAR scores warrant further comprehensive prospective studies.

Human post-implantation blastocyst-like characteristics of Muse cells isolated from human umbilical cord.

Muse cells, identified as cells positive for the pluripotent surface marker SSEA-3, are pluripotent-like endogenous stem cells located in the bone marrow (BM), peripheral blood, and organ connective tissues. The detailed characteristics of SSEA-3(+) cells in extraembryonic tissue, however, are unknown. Here, we demonstrated that similar to human-adult tissue-Muse cells collected from the BM, adipose tissue, and dermis as SSEA-3(+), human-umbilical cord (UC)-SSEA-3(+) cells express pluripotency markers, differentiate into triploblastic-lineage cells at a single cell level, migrate to damaged tissue, and exhibit low telomerase activity and non-tumorigenicity. Notably, ~ 20% of human-UC-SSEA-3(+) cells were negative for X-inactive specific transcript (XIST), a naïve pluripotent stem cell characteristic, whereas all human adult tissue-Muse cells are XIST-positive. Single-cell RNA sequencing revealed that the gene expression profile of human-UC-SSEA-3(+) cells was more similar to that of human post-implantation blastocysts than human-adult tissue-Muse cells. The DNA methylation level showed the same trend, and notably, the methylation levels in genes particularly related to differentiation were lower in human-UC-SSEA-3(+) cells than in human-adult tissue-Muse cells. Furthermore, human-UC-SSEA-3(+) cells newly express markers specific to extraembryonic-, germline-, and hematopoietic-lineages after differentiation induction in vitro whereas human-adult tissue-Muse cells respond only partially to the induction. Among various stem/progenitor cells in living bodies, those that exhibit properties similar to post-implantation blastocysts in a naïve state have not yet been found in humans. Easily accessible human-UC-SSEA-3(+) cells may be a valuable tool for studying early-stage human development and human reproductive medicine.

Flow shear force destabilizes carotid plaques by affecting CHOP and GRP78 proteins.

BACKGROUND: Various factors, including blood, inflammatory, infectious, and immune factors, can cause ischemic stroke. However, the primary cause is often the instability of cervical arteriosclerosis plaque. It is estimated that 18-25% of ischemic strokes are caused by the rupture of carotid plaque.1 Plaque stability is crucial in determining patient prognosis. Developing a highly accurate, non-invasive, or minimally invasive technique to assess carotid plaque stability is crucial for diagnosing and treating stroke.Previous research by our group has demonstrated that the expression levels of CHOP (C/EBP homologous protein) and GRP78 (glucose-regulated protein 78) are correlated with the stability of atherosclerotic plaques.2 OBJECT: This research assesses changes in GRP78 and CHOP expressions in human umbilical vein endothelial cells(HUVEC) following experiments within the hemodynamic influencing factors test system. Additionally, it includes conducting an empirical study on the impact of blood flow shear force on the stability of human carotid atherosclerotic plaques. The objective is to explore the implications of blood flow shear force on the stability of carotid atherosclerotic plaques. METHOD: The hemodynamic influencing factors test bench system was configured with low (Group A, 4 dyns/cm²), medium (Group B, 8 dyns/cm²), and high shear force groups (Group C, 12 dyns/cm²). Relative expression levels of GRP78 and CHOP proteins in human umbilical vein endothelial cells were measured using Western blot analysis, and quantitative analysis of GRP78 and CHOP mRNA was conducted using RT-qPCR. Meanwhile, plaques from 60 carotid artery patients, retrieved via Carotid Endarterectomy (CEA), were classified into stable (S) and unstable (U) groups based on pathological criteria. Shear force at the carotid bifurcation was measured preoperatively using ultrasound. Western blot and RT-qPCR were used to analyze the relative expression levels of GRP78 and CHOP proteins and mRNA, respectively, in the plaque specimens from both groups. RESULT: Expression levels of GRP78, CHOP proteins, and their mRNAs were assessed in groups A, B, and C via Western blot and RT-qPCR. Results showed that in the low-shear group, all markers were elevated in group A compared to groups B and C. Statistical analysis revealed significantly lower shear forces at the carotid bifurcation in group U compared to group S. In group U plaques, GRP78 and CHOP expressions were significantly higher in group U than in group S. CONCLUSION: Blood flow shear forces variably affect the expression of GRP78 and CHOP proteins, as well as their mRNA levels, in vascular endothelial cells. The lower the shear force and fluid flow rate, the higher the expression of GRP78 and CHOP, potentially leading to endoplasmic reticulum stress(ERS), which may destabilize the plaque.

Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus. / 人脐带间å 质干细胞通过IGF1R-CHK2-p53信号轴减轻2åž‹ç³–å°¿ç— é›„æ€§å¤§é¼ ç³–å°¿ç— è‚¾ç— .

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red "O" staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Effects of antenatal corticosteroids on fetal hemodynamics: a longitudinal study.

Objective: To study the effect of antenatal corticosteroid administration on fetal hemodynamics using longitudinal analysis of Doppler waveforms in the umbilical artery (UA) and middle cerebral artery (MCA). Materials and Methods: This was a retrospective study that included 30 fetuses at risk for preterm birth. Twenty-eight pregnant women were treated with betamethasone for fetal lung maturation. Doppler examinations of the UA and MCA were performed once before and three or eight times after corticosteroid administration. We used a Bayesian hierarchical linear model. Reference ranges were constructed, and associations between variables (gestational age and pre-eclampsia) were tested. Results: The mean maternal age, gestational age at betamethasone administration, and gestational age at delivery were 32.6 ± 5.89 years, 30.2 ± 2.59 weeks, and 32.9 ± 3.42 weeks, respectively. On UA Doppler, there was a significant decrease in the pulsatility index (PI) after corticosteroid administration, with a mean of 0.1147 (credibility interval: 0.03687-0.191) in three observations and a median of 0.1437 (credibility interval: 0.02509-0.2627) in eight observations. However, there was no significant change in the Doppler MCA PI, regardless of gestational age and the presence or absence of pre-eclampsia. Conclusion: Although antenatal corticosteroid administration induced a significant decrease in the Doppler UA PI, we observed no change in the cerebral vasculature.

Objetivo: Estudar o efeito da administração antenatal de corticosteroides na hemodinâmica fetal mediante análise longitudinal do Doppler na artéria umbilical (AU) e artéria cerebral média (ACM). Materiais e Métodos: Este foi um estudo retrospectivo que incluiu 30 fetos com risco de nascimento pré-termo. Vinte e oito gestantes foram tratadas com betametasona para maturação pulmonar fetal. Os exames de Doppler da AU e da ACM foram realizados uma vez antes e depois da administração de corticosteroides, num total de três ou oito observações. Utilizamos o modelo linear hierárquico com abordagem Bayesiana. Foram construídos os intervalos de referência e testadas associações entre variáveis (idade gestacional e pré-eclâmpsia). Resultados: A média ± desvio-padrão da idade materna, idade gestacional na administração de betametasona e idade gestacional no parto foram 32,6 ± 5,89 anos, 30,2 ± 2,59 semanas e 32,9 ± 3,42 semanas, respectivamente. No Doppler da AU, verificou-se diminuição significativa do índice de pulsatilidade (IP) com a terapêutica com corticosteroides (média: 0,1147 [0,03687-0,191]; em três observações) (mediana: 0,1437 [0,02509-0,2627]; em oito observações). No entanto, não foi observada alteração significativa no IP do Doppler da ACM, independentemente da idade gestacional e do diagnóstico de pré-eclâmpsia. Conclusão: Os corticosteroides pré-natais induziram diminuição significativa no IP do Doppler da AU, mas não houve alteração na vasculatura cerebral.

Moderate Prenatal Alcohol Exposure Increases Toll-like Receptor Activity in Umbilical Cord Blood at Birth: A Pilot Study.

The prevalence of prenatal alcohol exposure (PAE) is increasing, with evidence suggesting that PAE is linked to an increased risk of infections. PAE is hypothesized to affect the innate immune system, which identifies pathogens through pattern recognition receptors, of which toll-like receptors (TLRs) are key components. We hypothesized that light-to-moderate PAE would impair immune responses, as measured by a heightened response in cytokine levels following TLR stimulation. Umbilical cord samples (10 controls and 8 PAE) from a subset of the Ethanol, Neurodevelopment, Infant and Child Health Study-2 cohort were included. Peripheral blood mononuclear cells (PMBCs) were stimulated with one agonist (TLR2, TLR3, TLR4, or TLR9). TLR2 agonist stimulation significantly increased pro-inflammatory interleukin-1-beta in the PAE group after 24 h. Pro- and anti-inflammatory cytokines were increased following stimulation with the TLR2 agonists. Stimulation with TLR3 or TLR9 agonists displayed minimal impact overall, but there were significant increases in the percent change of the control compared to PAE after 24 h. The results of this pilot investigation support further work into the impact on TLR2 and TLR4 response following PAE to delineate if alterations in levels of pro- and anti-inflammatory cytokines have clinical significance that could be used in patient management and/or attention to follow-up.

Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling. AIM: To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved. METHODS: Human vaginal wall collagen content was assessed by Masson's trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed via RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined via functional experiments in vitro. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules. RESULTS: In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 µg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production in vitro. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression. CONCLUSION: HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.

Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy.

BACKGROUND: Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that affects premature infants. Although mounting evidence supports the therapeutic effect of exosomes on NEC, the underlying mechanisms remain unclear. AIM: To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell (UCMSCs) exosomes, as well as their potential in alleviating NEC in neonatal mice. METHODS: NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide (LPS), after which the mice received human UCMSC exosomes (hUCMSC-exos). The control mice were allowed to breastfeed with their dams. Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting. Colon tissues were collected from NEC neonates and analyzed by immunofluorescence. Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells. RESULTS: We found that autophagy is overactivated in intestinal epithelial cells during NEC, resulting in reduced expression of tight junction proteins and an increased inflammatory response. The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy. We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS. CONCLUSION: These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment. These findings also enhance our understanding of the role of the autophagy mechanism in NEC, offering potential avenues for identifying new therapeutic targets.

Human umbilical cord allograft associated with higher pediatric urethrocutaneous fistula repair success rates.

BACKGROUND: Urethrocutaneous fistula (UCF) formation is a known complication following hypospadias repair, affecting between 5 and 70% of cases. Moreover, approximately 30% of patients experience refistulization after UCF repair. The use of extracellular matrices, such as AmnioCord, a dehydrated human umbilical cord allograft manufactured by MiMedx®, may mitigate high rates of refistulization. OBJECTIVE: To determine whether the use of AmnioCord during UCF repair is associated with reduced incidence of subsequent UCFs among pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: Electronic medical records were retrospectively reviewed among 60 patients who underwent at least one UCF repair at a pediatric hospital in a large urban setting in the U.S. between January 2012-June 2018. Patients were followed through January 2024. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adjusted generalized estimating equation regression models were used to assess the association between AmnioCord use and rates of refistulization, while controlling for confounding variables. RESULTS: The number of fistula presentations per patient ranged from one to four; 53.3% had one fistula, 30.0% had two, and 16.6% had three or more. Overall fistula repair success rate was 56.8% but significantly differed by AmnioCord use in adjusted modelling; 69.4% of cases that received AmnioCord were successfully repaired, compared to 47.2% of cases that did not receive AmnioCord. In adjusted models, patients who received AmnioCord had 2.66 times greater odds of surgical success than patients who did not receive AmnioCord (95% CI:1.13-6.24; p = 0.02). CONCLUSIONS: This study demonstrates a positive association between AmnioCord use and successful UCF closure among pediatric patients.

Cord Obstruction and Delayed Cord Clamping Do Not Affect Gut Function in Neonatal Piglets.

INTRODUCTION: Birth-related obstruction of umbilical blood flow may induce hypoxic insults that affect postnatal organ adaptation. Using newborn cesarean-delivered pigs, we hypothesized that cord obstruction during delivery negatively affects physiological transition and gut maturation. Further, we investigated if delayed cord clamping (DCC) improves gut outcomes, including sensitivity to formula-induced necrotizing enterocolitis (NEC)-like lesions. METHODS: In experiment 1, preterm (n = 24) and near-term (n = 29) piglets were subjected to umbilical cord obstruction (UCO, 5-7 min in utero), with corresponding pigs delivered without obstruction (CON, n = 17-22). Experiment 2 assessed preterm pigs subjected to delayed cord clamping (n = 30, 60 s) or immediate cord transection with umbilical cord milking (UCM, n = 34). Postnatal vital parameters were recorded, together with a series of gut parameters after 3 days of formula feeding. RESULTS: UCO induced respiratory-metabolic acidosis in near-term pigs at birth (pH 7.16 vs. 7.32, pCO2 12.5 vs. 9.2 kPa, lactate 5.2 vs. 2.5 mmol/L, p < 0.05). In preterm pigs, UCO increased failure of resuscitation and mortality shortly after birth (88 vs. 47%, p < 0.05). UCO did not affect gut permeability, transit time, macromolecule absorption, six digestive enzymes, or sensitivity to NEC-like lesions. In experiment 2, DCC improved neonatal hemodynamics (pH 7.28 vs. 7.20, pCO2 8.9 vs. 9.9 at 2 h, p < 0.05), with no effects on gut parameters. CONCLUSION: UCO and DCC affect neonatal transition and hemodynamics, but not neonatal gut adaptation or sensitivity to NEC-like lesions. Our findings suggest that the immature newborn gut is highly resilient to transient birth-related changes in cord blood flow.

Prenatal diagnosis of the umbilical cord torsion at the placental cord insertion site: A case report and literature review.

A 35-year-old woman (gravida 1, para 0) was admitted to our hospital at 28 weeks' gestation with vaginal bleeding from placenta previa. Severe fetal bradycardia was observed during fetal heart rate monitoring. Ultrasonography showed widely dilated veins on the fetal surface of the placenta and an extraordinarily low umbilical artery peak systolic velocity in the Doppler study. Umbilical cord torsion was suspected. On the subsequent day, we performed a cesarean section due to worsening fetal heart rate patterns. Umbilical artery blood gas analysis indicated severe acidemia (pH 7.063), and umbilical cord torsion was confirmed at the placental cord insertion site. Diagnosing UCT prenatally is challenging; however, it can be suspected by scanning for the widely dilated veins on the fetal placental surface, termed as the "Sunset Sign," an abnormally low umbilical artery peak systolic velocity, and other fetal Doppler abnormalities.

Haplo-cord transplant. Realizing the potential of umbilical cord blood grafts. - A review of techniques and analysis of outcomes.

The combination of cord blood transplant with progenitor cells from partially HLA-matched adult donors (haplo-cord transplant) has been used over the past two decades. In Europe and the US the adult donor graft is CD34 selected and provides early hematopoiesis, but durable engraftment derives from the cord blood graft (CD34 selected haplo-cord). Neutrophil recovery is prompt and rates of acute and chronic GVHD are low. Recent Chinese studies combine cord blood grafts with T-replete haplo-identical grafts (unmodified haplo-cord). The haplo graft usually establishes dominance and UCB chimerism is rarely detected. Comparison studies suggest considerably decreased rates of relapse and improved outcomes, compared with either haplo-identical transplant or CBU transplant, particularly in patients with advanced leukemia. A recent prospective randomized study confirms this. Haplo-cord mitigates the engraftment delay of UCB transplant. The unique biology of UCB grafts results in low GVHD and improved GVL especially beneficial in high-risk disease.

Enhancement of endothelial function and attenuation of portal vein injury using mesenchymal stem cells carrying miRNA-25-3p.

The aims of this study were to determine whether human umbilical cord mesenchymal stem cells (hucMSCs) modified by miRNA-25-3p (miR-25-3p) overexpression could promote venous endothelial cell proliferation and attenuate portal endothelial cell injury. HucMSCs and human umbilical vein endothelial cells (HUVEC) were isolated and cultured from human umbilical cord and characterized. Lentiviral vectors expressing miRNA-25-3p were transfected into hucMSCs and confirmed by PCR. We verified the effect of miR-25-3p-modified hucMSCs on HUVEC by cell co-culture and cell supernatant experiments. Subsequently, exosomes of miR-25-3p-modified hucMSCs were isolated from cell culture supernatants and characterized by WB, NTA and TEM. We verified the effects of miR-25-3p-modified exosomes derived from hucMSCs on HUVEC proliferation, migration, and angiogenesis by in vitro cellular function experiments. Meanwhile, we further examined the downstream target genes and signaling pathways potentially affected by miR-25-3p-modified hucMSC-derived exosomes in HUVEC. Finally, we established a rat portal vein venous thrombosis model by injecting CM-DiR-labeled hucMSCs intravenously into rats and examining the homing of cells in the portal vein by fluorescence microscopy. Histological and immunohistochemical experiments were used to examine the effects of miRNA-25-3p-modified hucMSCs on the proliferation and damage of portal vein endothelial cells. Primary hucMSCs and HUVECs were successfully isolated, cultured and characterized. Primary hucMSCs were modified with a lentiviral vector carrying miR-25-3p at MOI 80. Co-culture and cell supernatant intervention experiments showed that overexpression of miRNA-25-3p in hucMSCs enhanced HUVEC proliferation, migration and tube formation in vitro. We successfully isolated and characterized exosomes of miR-25-3p-modified hucMSCs, and exosome intervention experiments demonstrated that miR-25-3p-modified exosomes derived from hucMSCs similarly enhanced the proliferation, migration, and angiogenesis of HUVECs. Subsequent PCR and WB analyses indicated PTEN/KLF4/AKT/ERK1/2 as potential pathways of action. Analysis in a rat portal vein thrombosis model showed that miR-25-3p-modified hucMSCs could homing to damaged portal veins. Subsequent histological and immunohistochemical examinations demonstrated that intervention with miR-25-3p overexpression-modified hucMSCs significantly reduced damage and attenuated thrombosis in rat portal veins. The above findings indicate suggest that hucMSCs based on miR-25-3p modification may be a promising therapeutic approach for use in venous thrombotic diseases.

Research progress and prospects of benefit-risk assessment methods for umbilical cord mesenchymal stem cell transplantation in the clinical treatment of spinal cord injury.

Over the past decade, we have witnessed the development of cell transplantation as a new strategy for repairing spinal cord injury (SCI). However, due to the complexity of the central nervous system (CNS), achieving successful clinical translation remains a significant challenge. Human umbilical cord mesenchymal stem cells (hUMSCs) possess distinct advantages, such as easy collection, lack of ethical concerns, high self-renewal ability, multilineage differentiation potential, and immunomodulatory properties. hUMSCs are promising for regenerating the injured spinal cord to a significant extent. At the same time, for advancing SCI treatment, the appropriate benefit and risk evaluation methods play a pivotal role in determining the clinical applicability of treatment plans. Hence, this study discusses the advantages and risks of hUMSCs in SCI treatment across four dimensions-comprehensive evaluation of motor and sensory function, imaging, electrophysiology, and autonomic nervous system (ANS) function-aiming to improve the rationality of relevant clinical research and the feasibility of clinical translation.

Acute abdomen secondary to ovarian tumour incarcerated in an umbilical hernia: A case report.

Acute abdomen due to incarcerated umbilical hernia is a surgical emergency. Acute abdomen secondary to gynaecological conditions is not uncommon. However, acute abdomen due to incarceration of a gynaecological tumour in an umbilical hernia is rare. A 25-year-old nullipara was admitted to the accident and emergency unit with a history of recurrent lower abdominal pain and abdominal swelling for 4 weeks. Pain worsened within the last 24 h necessitating presentation. Examination revealed a low-grade pyrexia, tachypnoea, an umbilical swelling with generalised abdominal tenderness, and a pelvic mass more in the right iliac fossa. Bedside abdomino-pelvic ultrasound scan confirmed bilateral adnexal masses with features suggestive of mature teratoma. A diagnosis of acute abdomen secondary to ovarian tumour accident was made. An emergency exploratory laparotomy revealed a huge right ovarian tumour incarcerated in an umbilical hernia. She had bilateral ovarian cystectomy and herniorrhaphy. Gynaecological tumours presenting as incarcerated or strangulated hernias are extremely rare but can be a cause of acute abdomen in women.

Understanding the Spectrum of Flood Syndrome: A Case Series.

Flood syndrome refers to ruptured umbilical hernias in patients with chronic ascites with underlying liver cirrhosis. These ruptures may introduce infection into the abdomen and hence require emergency surgery. However, these patients are at high risk during these procedures owing to coagulopathy, hypotension and electrolyte imbalances. In our series, we describe six patients who presented with varying degrees of severity and were treated with a standardised protocol of primary anatomic repair and drain placement. Furthermore, we assessed the Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores in these patients and correlated them to postoperative outcomes. This surgical technique has a good outcome in patients whose CTP and MELD scores predict a safe postoperative period.