Umbilical Cord Research Articles

Myocardial infarction in rats was alleviated by MSCs derived from the maternal segment of the human umbilical cord.

Mesenchymal stem cells (MSCs) are safe and effective in treating myocardial infarction (MI) and have broad application prospects. However, the heterogeneity of MSCs may affect their therapeutic effect on the disease. We recently found that MSCs derived from different segments of the same umbilical cord (UC) showed significant difference in the expression of genes that are related to heart development and injury repair. We therefore hypothesized that those MSCs with high expression of above genes are more effective to treat MI and tested it in this study. MSCs were isolated from 3cm-long segments of the maternal, middle and fetal segments of the UC (maternal-MSCs, middle-MSCs and fetal-MSCs, respectively). RNA-seq was used to analyze and compare the transcriptomes. We verified the effects of MSCs on oxygen-glucose deprivation (OGD)-induced cardiomyocyte apoptosis in vitro. In vivo, a rat MI model was established by ligating the left anterior descending coronary artery, and MSCs were injected into the myocardium surrounding the MI site. The therapeutic effects of MSCs derived from different segments of the UC were evaluated by examining cardiac function, histopathology, cardiomyocyte apoptosis, and angiogenesis. Compared to fetal-MSCs and middle-MSCs, maternal-MSCs exhibited significantly higher expression of genes that are associated with heart development, such as GATA-binding protein 4 (GATA4), and myocardin (MYOCD). Coculture with maternal-MSCs reduced OGD-induced cardiomyocyte apoptosis. In rats with MI, maternal-MSCs significantly restored cardiac contractile function and reduced the infarct size. Mechanistic experiments revealed that maternal-MSCs exerted cardioprotective effects by decreasing cardiomyocyte apoptosis, and promoting angiogenesis. Our data demonstrated that maternal segment-derived MSCs were a superior cell source for regenerative repair after MI. Segmental localization of the entire UC when isolating hUCMSCs was necessary to improve the effectiveness of clinical applications.

Revisiting the human umbilical cord epithelium. An atypical epithelial sheath with distinctive features.

The umbilical cord epithelium (UCE) is the surface tissue that covers the umbilical cord (UC). It is widely considered a single-layered epithelium composed of squamous or cuboidal cells, which are in constant contact with amniotic fluid. The objective of this study was to elucidate the distinctive structural characteristics and abundance of specific proteins in this unique epithelium, many of which have not been previously demonstrated. Samples of the UC were obtained from term pregnancies (n = 12) and processed for examination using stereo, light, electron, and 3D high-resolution confocal microscopy. Sections displayed a range of stratification, ranging from a single squamous layer to 4-5 layers of round/cuboid cells, challenging the notion of considering it as a single-layered structure. Cells are located on a well-developed basement membrane (BM), as evidenced by the expression of BM-specific proteins and PAS staining. The cells possess distinctive cytoplasmic domains that are tightly bound to each other by desmosomes and interdigitating anchoring surfaces. Desquamations and limited organelles suggest that the cells have reached the final stages of differentiation and are no longer actively synthesizing proteins, despite maintaining stratification-specific expression levels of cytoskeletal, junctional, receptor, and stem cell proteins. Although definitive keratinization was not observed, the distribution of proteins and the distinctive structural organization of the single/multi-layered cells suggest that they exhibit plasticity, likely due to adaptive mechanisms in response to chemical and/or mechanical stimuli during fetal development. These structural alterations may facilitate the active transportation of soluble ingredients between the amniotic fluid and cord blood through an intercellular route.

Mitochondrial DNA copy number and neurocognitive outcomes in children.

Low mitochondria DNA copy number (mtDNAcn) has been linked to cognitive decline. However, the role of mtDNAcn in healthy cognitive development is unclear. We hypothesized early-life mtDNAcn would be associated with children's learning and memory. We quantified mtDNAcn in umbilical cord blood and child blood at ages 5-7 from participants in a prospective birth cohort. We administered the Children's Memory Scale (CMS) at ages 9-14 (N = 342) and the Wechsler Intelligence Scale for Children (WISC-IV) at ages 7 and 9 (N = 457). Associations between mtDNAcn tertiles and CMS and WISC were evaluated with linear regression and linear mixed-effects models, respectively. We examined non-linear associations using generalized additive mixed models. Relative to the middle tertile of mtDNAcn, lower childhood mtDNAcn was associated with lower WISC Working Memory (β = -2.65, 95% CI [-5.24, -0.06]) and Full-Scale IQ (β = -3.71 [-6.42, -1.00]), and higher CMS Visual Memory (β = 4.70 [0.47, 8.93]). Higher childhood mtDNAcn was linked to higher CMS Verbal Memory (β = 7.75 [2.50, 13.01]). In non-linear models, higher childhood mtDNAcn was associated with lower WISC Verbal Comprehension. Our study provides novel evidence that mtDNAcn measured in childhood is associated with children's neurocognitive performance. mtDNAcn may be a marker of healthy child development. Mitochondrial DNA copy number (mtDNAcn) may serve as a biomarker for early-life neurocognitive performances in the children's population. Both low and high mtDNAcn may contribute to poorer neurocognition, reflected through learning and memory abilities. This research elucidated the importance of investigating mitochondrial biomarkers in healthy populations and facilitated advancements of future studies to better understand the associations between mitochondrial markers and adverse children's health outcomes.

A girl with a novel nonsense mutation in Chediak-Higashi syndrome was relieved successfully by treatment with HCST and UCBT: a case report.

Chediak-Higashi syndrome (CHS) is a life-threatening autosomal recessive immunodeficiency disease presenting with recurrent infections, hypopigmentation, progressive neurodegeneration, and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated stage. Two-thirds of patients experience a fatal accelerated phase. CHS is caused by lysosomal transport regulator (LYST) gene mutations. We report the case of CHS, who was born with pale skin and silver hair. Bone marrow aspirate revealed large inclusions in granulocytes, monocytes, and lymphocytes. Genetic analysis revealed a new nonsense mutation in the LYST gene: c.8186G > A (W2729Ter). The child presented with fever, hepatosplenomegaly, and lymphadenectasis. Laboratory tests showed pancytopenia, hypofibrinogenemia, and high serum ferritin, indicating an accelerated phase of CHS. She underwent allogeneic hematopoietic stem cell transplantation (HCST) combined with umbilical cord blood transplantation (UCBT) after HLH-related chemotherapy. The patient has been alive for nine months without recurrence. We have identified a novel nonsense mutation in the LYST gene that correlates with a severe phenotype, and HSCT combined with UCBT is an effective treatment.

Intraovarian injection of 3D-MSC-EVs-ECM gel significantly improved rat ovarian function after chemotherapy

BackgroundRestoring the function of the ovary is important for chemotherapy-induced ovarian failure (COF) patients. Stem cell and extracellular vesicles (EVs) therapy show promise but need further improvement.MethodsHuman umbilical cord mesenchymal stem cells (hUC-MSCs) were primarily cultured and further three-dimensional (3D) cultured using an ultra-low attachment surface method. The expression levels of nutritional cytokines and immunomodulatory and stemness-related genes of 3D-cultured hUC-MSCs were analyzed. EVs were isolated by ultracentrifugation and characterized. Ovaries were decellularized with sodium dodecyl sulfate to obtain extracellular matrix (ECM). Lyophilized EVs from three-dimensional (2D) or 3D hUC-MSCs were mixed with ECM to prepare the 2D/3D-MSC-EVs-ECM gels. The therapeutic effect of the MSC-EVs-ECM gel on cyclophosphamide (CTX) -treated rats was analyzed through various tests. RNA sequencing was used to analyze the expression changes of genes before and after treatment.ResultsAfter culturing in ultra-low attachment dishes, hUC-MSCs aggregated into spheroids and significantly upregulated the expression levels of immunomodulatory and stemness-related genes. The total EVs yield was also upregulated (5.6-fold) after 3D culture. The cell viability of CTX-treated ovarian granulosa cells (OGCs) was significantly rescued by coculture with the 3D-MSC-EVs-ECM gel. Hormones indicative of ovarian function, AMH, E2, and FSH, were recovered in both the CTX + 2D-MSC-EVs-ECM gel group and the CTX + 3D-MSC-EVs-ECM gel group, while the apoptosis-related protein Bax was significantly downregulated. The 3D-MSC-EVs-ECM gel was more effective than the 2D-MSC-EVs-ECM gel. Significantly differentially expressed genes, such as Hbb-b1, Gpd1, and Sirpa, were detected by RNA sequencing. Hbb-b1 was increased in the ovaries of CTX-treated rats, and this increase was attenuated by injecting the 2D/3D-MSC-EVs-ECM gel. Gpd1 was increased after CTX treatment, and this increase was reversed by the 3D-MSC-EVs-ECM gel. Sirpa was decreased in the ovaries of CTX-treated rats, and this decrease was attenuated by injecting the 3D-MSC-EVs-ECM gel.ConclusionsOur study demonstrated that the 3D-MSC-EVs-ECM gel is an efficient strategy for the recovery of ovarian function in CTX-induced ovarian failure.

Adverse pregnancy outcomes and the abnormal umbilical cord coiling index.

The abnormal umbilical cord coiling index (UCI) may be one of the ways to predict adverse pregnancy outcomes. This study attempted to determine the association between abnormal UCI and maternal, fetal, and neonatal outcomes. This longitudinal study was conducted on 400 women referred for delivery from April to August 2021. UCI was calculated by dividing the total number of coils by the total length of the umbilical cord in centimeters. In eligible cases, the length of the umbilical cord and the number of vascular coils along the total umbilical cord were measured after birth. UCI less than the 10th percentile and more than the 90th percentile was considered abnormal, and between the 10th and 90th percentiles was considered normal. Data were analyzed using SPSS version 20. P < 0.05 were considered statistically significant. The mean length of the umbilical cord was 56.12±8.38 cm, the number of umbilical cord rings was 13.70±3.51, and the UCI was 0.24±0.07. In the regression analysis, women with gestational diabetes had a significant association with abnormal UCI (P = 0.044). Thus, the probability of abnormal UCI was about 3.5 times higher in women with gestational diabetes than in normal pregnancies. Also, the history of stillbirth had a significant association with abnormal UCI (P < 0.05). It is recommended to perform a UCI examination after delivery as part of a neonatal examination to find an explanation for maternal, fetal, and neonatal outcomes.

HUMAN IMMUNODEFICIENCY VIRUS’ EXPOSED UNINFECTED NEWBORNS: A VULNERABLE POPULATION WITH SOME DEFECTIVE IMMUNE SYSTEM ELEMENTS AT BIRTH IN YAOUNDE-CAMEROON, CENTRAL AFRICA

Abstract Introduction/Objective The reduction in vertical transmission of human immunodeficiency virus (HIV) in Cameroon, thanks to the success of Option B+ prevention measures, has favored the increase in the rate of HIV exposed uninfected (HEU) infants. The latter, however, present a threefold higher morbidity and mortality than their HIV unexposed and uninfected (HUU) counterparts. With multiple causes, a dysfunction of the immune system would be incriminated but the evidence to demonstrate this and to advocate for a specific follow-up is lacking. This study objective was to determine the effect of in utero exposure to HIV-1 on certain immune elements of HEU newborns. Methods/Case Report A Case-control study was carried out in three reference hospitals in Yaounde. From June 2022 to July 2023, demographical characteristics of 62 HEU newborns of positive parturients with undetectable viral load who gave their consent (cases), and 65 HUU (controls) were taken. Then samples of umbilical cord blood were collected under ethical authorization no. BTC-JIRB2022-021. Then, blood count and differential leukocytes count were performed using DF55 DEMIND and May-Grünwald Giemsa Kit. Excel 2007 and R v4.1.3 softwares were used to record and analyze the data, with significance level for a p-value &amp;lt; 0.05. Results (if a Case Study enter NA) The average APGAR vitality score (appearance, pulse, grimace, activity, respiration) at 1, 5 and 10 min of life was reduced, but not significantly (p = 0.3) in the HEU (8/10, 9/10 and 10/10), compared to the HUU (9/10, and 10/10); as well as head circumference: (33.16 ± 1.64) cm and (34.8 ± 1.52) cm (p = 0.8) respectively. Unlike leukopenia (p=0.24), umbilical monocytosis (p=0.04) and lymphopenia (p=0.001) were significantly linked to HIV exposure in HEU, signs of inflammation from birth. Conclusion HIV exposed uninfected newborns present a drop in immunity and an inflammatory sign at birth, materialised clinically and biologically with a highly significant lymphopenia.

Overexpression of USP35 enhances the protective effect of hUC-MSCs and their extracellular vesicles in oxygen-glucose deprivation/reperfusion-induced SH-SY5Y cells via stabilizing FUNDC1

Ischemia-reperfusion (IR) injury is associated with neurological disorders such as stroke. The therapeutic potential of human umbilical cord mesenchymal stem cells (hUC-MSCs) and their secreted extracellular vesicles (EVs) in alleviating IR injury across various cell types including neuronal cells has been documented. However, the underlying mechanisms through which hUC-MSCs and hUC-MSC-EVs protect neuronal cells from IR-triggered damage are not well understood. In this study, we co-cultured SH-SY5Y neuroblastoma cells with hUC-MSCs or hUC-MSC-EVs and subjected them to oxygen-glucose deprivation/reperfusion (OGD/R) treatment. Our findings indicate that both hUC-MSCs and hUC-MSC-EVs significantly improved viability, reduced apoptosis, promoted autophagy of OGD/R-induced SH-SY5Y cells, and decreased mitochondrial reactive oxygen species levels within them. Furthermore, the neuroprotective effect of hUC-MSCs and hUC-MSC-EVs in OGD/R-induced SH-SY5Y cells was enhanced by overexpressing USP35, a deubiquitinase. Mechanistically, USP35 interacted with and stabilized FUNDC1, a positive regulator of mitochondrial metabolism. Knockdown of FUNDC1 in USP35-overexpressing hUC-MSCs and their secreted EVs eliminated the augmented neuroprotective function induced by excess USP35. In conclusion, these findings underscore the crucial role of USP35 in enhancing the neuroprotective function of hUC-MSCs and their secreted EVs, achieved through the stabilization of FUNDC1 in OGD/R-induced SH-SY5Y cells.

Study of Some Apoptotic Protein Expration in Human Mesenchymal Stem Cells During Toxoplasma Gondii Infection

Background: Toxoplasma gondii (T. gondii) infection is a significant health concern, particularly during pregnancy, as it can lead to fetal harm and birth abnormalities. Specific Background: The role of apoptosis in managing T. gondii infection remains poorly understood, particularly regarding its molecular mechanisms. Knowledge Gap: The impact of T. gondii infection on apoptosis in mesenchymal stem cells (MSCs) derived from human umbilical cords has not been thoroughly studied in existing literature. Aims: This study aimed to investigate the activation of apoptosis and its regulatory mechanisms in human Wharton’s Jelly mesenchymal stem cells (WJ-MSCs) during T. gondii infection. Results: Using non-enzymatic techniques, we isolated T. gondii from infected and aborted phase-specific placentas. Our findings demonstrated a significant increase in the expression of apoptosis-activating genes (CASP2, CASP3, Bak1) in WJ-MSCs following infection, with a marked decrease in cell viability observed within 2 to 4 hours of exposure to the parasite (P≤0.05). Novelty: This study provides novel insights into the relationship between T. gondii infection and apoptosis in WJ-MSCs, highlighting the specific gene expression changes that occur in response to infection. Implications: Research on T. gondii's apoptotic pathways is crucial for developing therapeutic strategies to mitigate pregnancy-related adverse effects and improve maternal and fetal health outcomes. Highlights: Increased Apoptosis: T. gondii enhances apoptosis in mesenchymal stem cells. Cell Viability Impact: Significant decrease in WJ-MSC viability after infection. Clinical Relevance: Insights can inform strategies to reduce fetal infection risks. Keywords: Toxoplasma gondii, apoptosis, Wharton’s Jelly mesenchymal stem cells, pregnancy, gene expression

From banked human cord blood to induced pluripotent stem cells: New opportunities and promise in induced pluripotent stem cell banking (Review).

Umbilical cord blood (CB) is a valuable source of haematopoietic stem/progenitor cells (HSCs) and is known for the therapeutic use of these cells in treating blood disorders. However, challenges such as a high running cost and the increasing availability of treatment alternatives have made the effort to sustain CB banks difficult. This prompts the need to revisit the current CB banking initiatives to retain the relevance in this ever‑changing era parallel to the fast‑pacing development of cell‑based therapeutic technology. Cellular reprogramming has shown to have successfully converted adult somatic cells into human induced pluripotent stem cells (hiPSCs), which promise wider applications in regenerative medicine, personalized treatment and tissue engineering. CB is the youngest, primitive adult cell source that has not been affected by any prior, acquired disorders. Hence, using CB as a source of candidate cells for generating hiPSCs may be a new opportunity for banking, albeit with challenges. The present review summarizes the rise and fall of CB usage and banking for clinical therapy, the considerations in reprogramming CB into hiPSCs, the safety concerns regarding the use of hiPSC‑derived cells in clinical transplantation and the prospect of using CB‑derived hiPSCs.

Safety of the use of dinoprostone gel and vaginal insert for induction of labor: A multicenter retrospective cohort study.

To assess adverse obstetric and neonatal outcomes associated with the use of dinoprostone for induction of labor, with particular attention on categories for which caution is recommended by the Italian Medicines Agency and the European Medicine Agency. A retrospective multicenter observational study was conducted on a population of 1687 patients undergoing induction of labor with vaginal dinoprostone (gel or insert) between August 2019 and June 2022. Patients were subdivided based on maternal age, gestational age, and obstetric disorders. Data regarding the mode of delivery, the incidence of tachysystole, and the obstetric and perinatal outcomes were collected. The main adverse event associated with the use of dinoprostone was tachysystole. However, tachysystole was not associated with an increased risk of cesarean section (CS), neonatal intensive care (NICU) admission, low 1-min Apgar, or umbilical cord acidosis. Maternal age greater than 35 years, gestational age greater than 40 weeks, and obstetric disorders were not associated with an increased rate of tachysystole, NICU admission, low 1- and 5-min Apgar scores, and cord acidosis. The only associated adverse outcomes in those categories were postpartum hemorrhage with age greater than 35 years and tachysystole with gestational diabetes mellitus and hypertensive disorders. Not a single case of severe outcome (disseminated intravascular coagulation, uterine rupture, maternal and fetal death) was reported in the cohort. Providing there is adequate maternal and fetal surveillance, in an inpatient setting, dinoprostone could be safely administered for the induction of labor and considered appropriate in high-risk pregnancies. Tachysystole can be self-identified by the patient and effectively managed.

Nose-to-brain delivery of stem cells in stroke: the role of extracellular vesicles.

Stem cell transplantation offers a promising therapy that can be administered days, weeks, or months after a stroke. We recognize 2 major mitigating factors that remain unresolved in cell therapy for stroke, notably: (1) well-defined donor stem cells and (2) mechanism of action. To this end, we advance the use of ProtheraCytes, a population of non-adherent CD34+ cells derived from human peripheral blood and umbilical cord blood, which have been processed under good manufacturing practice, with testing completed in a phase 2 clinical trial in post-acute myocardial infarction (NCT02669810). We also reveal a novel mechanism whereby ProtheraCytes secrete growth factors and extracellular vesicles (EVs) that are associated with angiogenesis and vasculogenesis. Our recent data revealed that intranasal transplantation of ProtheraCytes at 3 days after experimentally induced stroke in adult rats reduced stroke-induced behavioral deficits and histological damage up to 28 days post-stroke. Moreover, we detected upregulation of human CD63+ EVs in the ischemic brains of stroke animals that were transplanted with ProtheraCytes, which correlated with increased levels of DCX-labeled neurogenesis and VEGFR1-associated angiogenesis and vasculogenesis, as well as reduced Iba1-marked inflammation. Altogether, these findings overcome key laboratory-to-clinic translational hurdles, namely the identification of well-characterized, clinical grade ProtheraCytes and the elucidation of a potential CD63+ EV-mediated regenerative mechanism of action. We envision that additional translational studies will guide the development of clinical trials for intranasal ProtheraCytes allografts in stroke patients, with CD63 serving as a critical biomarker.

Evaluation of Safety and Efficacy of Cell Therapy Based on Osteoblasts Derived from Umbilical Cord Mesenchymal Stem Cells for Osteonecrosis of the Femoral Head: Study Protocol for a Single-Center, Open-Label, Phase I Clinical Trial.

Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 × 107 hUC-O cells, n = 3), medium-dose (2 × 107 cells, n = 3), and high-dose group (4 × 107 cells, n = 3) in the order of their arrival at the facility, and, depending on the occurrence of dose-limiting toxicity, up to 18 patients can be enrolled by applying the 3 + 3 escalation method. We will perform hUC-O (CF-M801) transplantation combined with core decompression and follow-up for 12 weeks according to the study protocol. Safety will be determined through adverse event assessment, laboratory tests including a panel reactive antibody test, vital sign assessment, physical examination, and electrocardiogram. Efficacy will be explored through the change in pain visual analog scale, Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, ARCO stage, and also size and location of necrotic lesion according to Japanese Investigation Committee classification before and after the procedure. Joint preservation is important, particularly in younger, active patients with ONFH. Confirmation of the safety and efficacy of hUC-Os will lead to a further strategy to preserve joints for those suffering from ONFH and improve our current knowledge of cell therapy.

A patch comprising human umbilical cord-derived hydrogel and mesenchymal stem cells promotes pressure ulcer wound healing

Pressure ulcers (PUs) are common skin injuries known for their high morbidity, rapid onset, susceptibility to infection, and challenging healing process. One potential therapy for PUs is cell-based therapy using mesenchymal stem cells (MSCs). However, poor survival and low cell retention of MSCs on skin lesions limit their therapeutic effects and applications. In this study, we prepared an extracellular matrix (dECM) hydrogel decellularized from the human umbilical cord (UC). A patch composed of UC-dECM and UC-MSCs was employed in the treatment of PUs in C57BL/6 mice. Our results indicate that the UC-dECM hydrogel effectively sustains cell viability, enhances the stemness-related gene expression in UC-MSCs, and promotes human umbilical vein endothelial cells (HUVECs) migration and angiogenesis. Compared to the groups treated with the patch containing only UC-dECM, injection of UC-MSCs or gauze dressing, the patch combining UC-dECM hydrogel with UC-MSCs significantly accelerated PU healing. This positive outcome can be attributed to the promotion of tissue re-epithelialization, collagen deposition, angiogenesis, and inflammation inhibition. Our results suggest that the composite patch, comprised of UC-dECM hydrogel and UC-MSCs, may be a promising therapeutic approach for PU treatment.

Oxygenation associated with cord management strategies among preterm infants

Compare changes in SpO2 and FiO2 post-birth among preterm infants after delayed cord clamping (DCC), umbilical cord milking (UCM) or early cord clamping (ECC). Retrospective study of infants <32 weeks gestation born between 2014 and 2021. ECC was clamping 0-59 s, DCC was clamping ≥60 s after delivery, UCM defined as milking the intact umbilical cord several times before clamping. Of 463 infants; 257 received DCC, 168 received UCM, 38 received ECC. UCM infants had higher median SpO2 values at 4-(79% UCM vs 69% DCC, p = 0.027) and 5-(85% UCM vs 80% DCC, p = 0.023) minutes after-birth compared to DCC. DCC and UCM infants required lower FiO2 levels in the first 5-minutes compared to ECC infants (DCC 0.38 ± 0.17, UCM 0.40 ± 0.20 vs ECC 0.51 ± 0.27, p's <0.001). The proportion of infants achieving SpO2 ≥ 80% by 5 min was similar in all groups, FiO2 needed to achieve this goal was higher in ECC infants.

Decellularized umbilical cord wrapped with conductive hydrogel for peripheral nerve regeneration

Decellularized umbilical cord wrapped with conductive hydrogel for peripheral nerve regeneration

Maternal Obesity Alters Placental and Umbilical Cord Plasma Oxidative Stress, a Cross-Sectional Study.

Maternal obesity has been shown to impair the oxidative status in the placenta and newborns, potentially leading to adverse pregnancy outcomes and long-term effects on the programming of offspring metabolic status. This study aimed to investigate the impact of maternal obesity on maternal and umbilical cord plasma oxidative status, as well as placental oxidative adaptation. Maternal obesity (n = 20), defined as a pre-pregnancy BMI ≥ 25 kg/m2, and maternal leanness (n = 20), defined as a pre-pregnancy BMI < 23 kg/m2, were the group categories used in this study. Both groups were matched according to gestational age at delivery. Maternal blood, umbilical cord blood, and placental tissue were collected to assess nutritional content (cholesterol, triglyceride, and protein), oxidative stress markers (MDA and protein carbonyl), and antioxidant activity (SOD and catalase). Placental protein expression (SOD2, catalase, UCP2, and Nrf2) was evaluated using Western blot analysis. Catalase activity in maternal plasma significantly increased in the maternal obesity group (p = 0.0200), with a trend toward increased MDA and protein carbonyl levels. In umbilical cord plasma, triglyceride, protein carbonyl, and catalase activity were significantly elevated in the maternal obesity group compared with the lean controls (p = 0.0482, 0.0291, and 0.0347, respectively). Placental protein expression analysis revealed significantly decreased SOD2 (p = 0.0011) and catalase (p < 0.0001), along with Nrf2 downregulation (p < 0.0001). An increase in mitochondrial antioxidant UCP2 expression was observed (p = 0.0117). The neonatal protein carbonyl levels positively correlated with placental protein carbonyl (r = 0.7405, p < 0.0001) and negatively correlated with maternal catalase activity (r = -0.4332, p = 0.0052). This study thus provides evidence that maternal obesity is associated with placental and fetal oxidative stress, alongside a concurrent increase in placental antioxidant UCP2 expression.

Extraembryonic mesoderm cells derived from human embryonic stem cells rely on Wnt pathway activation.

Extraembryonic mesoderm cells (EXMCs) are involved in the development of multiple embryonic lineages and umbilical cord formation, where they subsequently develop into mesenchymal stem cells (MSCs). Although EXMCs can be generated from human naïve embryonic stem cells (ESCs), it is unclear whether human primed ESCs (hpESCs) can differentiate into EXMCs that subsequently produce MSCs. The present report described a three-dimensional differentiation protocol to induce hpESCs into EXMCs by activating the Wnt pathway using CHIR99021. Single-cell transcriptome and immunostaining analyses revealed that the EXMC characteristics were similar to those of post-implantation embryonic EXMCs. Cell sorting was used to purify and expand the EXMCs. Importantly, these EXMCs secreted extracellular matrix proteins, including COL3A1 and differentiated into MSCs. Inconsistent with other MSC types, these MSCs exhibited a strong differentiation potential for chondrogenic and osteogenic cells and lacked adipocyte differentiation. Together, these findings provided a protocol to generate EXMCs and subsequent MSCs from hpESCs.

THE POSSIBILITY OF DONATION OF ORGANS AND TISSUES

Organ and tissue donation is a very important subject in our society in general. I intend to discuss what organ donation is. The importance of organ and tissue donation. About the importance of awareness. Organ or tissue donation is an act by which the living individual decides to help in the treatment of other people. Donation may be from organs (kidney, liver, heart, pancreas and lung) or tissue (cornea, skin, bones, heart valves, cartilage, bone marrow and umbilical cord blood). The donation of organs such as the kidney, part of the liver and bone marrow can be done in life. For the donation of organs of deceased persons, only after the confirmation of the diagnosis of brain death can the procedure be performed. The most common is that it happens to people who suffer some kind of accident that causes head trauma, or who are victims of a stroke (stroke) and evolved to brain death. To understand the transplantation of the organs it is necessary to emphasize that the right to separate parts of the living or dead body integrate the personality, according to the understanding of Maria Helena Diniz (2006, p.249). Most of the time, organ transplantation may be the only life expectancy or the opportunity for a fresh start to about 40,000 patients waiting in the queue for Brazil. The gesture of family members who lose a loved one and decide to donate is an act of life, altruism and generosity, as a single donor can benefit at least ten people and make the difference between life and death. Brazil has the largest public transplant system in the world, responsible for financing about 95% of transplants. It is the second country in absolute number of transplants, behind only the United States.

Characterization of human placental fetal vessels in gestational diabetes mellitus.

Gestational diabetes mellitus is one of the most common complications during pregnancy. Its prevalence is rapidly increasing worldwide. Gestational diabetes mellitus is leading to an elevated risk for the development of endothelial dysfunction and cardiovascular diseases both in the mother and the child in later life. The underlying pathophysiological mechanisms are not well-understood. Therefore, we aimed to characterize the endothelial function in fetal placental vessels from mothers with gestational diabetes mellitus. In this study, we distinguished between insulin-treated and diet-controlled gestational diabetes mothers and compared them to a normoglycemic control group. The clinical data confirmed pre-conceptional overweight as a risk factor in women with insulin-treated gestational diabetes mellitus. The insulin-treated gestational diabetes group was also characterized by a recent family history of diabetes compared to mothers of the control or diet-controlled gestational diabetes group. Analyses of blood serum from umbilical cords suggested a reduced fetal insulin metabolism in the insulin-treated gestational diabetes group. Vascular function analysis in fetal placental vessels revealed an altered substance P-induced vasorelaxation in vessels from patients with insulin-dependent gestational diabetes. Inhibition of nitric oxide synthase affected only fetal vessel segments from the control group or diet-controlled gestational diabetes group, but not from insulin-dependent gestational diabetes. Finally, we found a significantly decreased substance P receptor (TACR1) mRNA expression in fetal vessel segments from patients with insulin-treated gestational diabetes. In conclusion, we provide evidence that different pathophysiological mechanisms might be responsible for the development of insulin-treated versus diet-controlled gestational diabetes. Only in fetal vessels from patients with insulin-treated gestational diabetes were we able to detect an endothelial dysfunction and a reduced fetal insulin conversion. This provides novel insights into the pathophysiology of the subtypes of gestational diabetes.