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Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-EVs) are valuable in nanomedicine as natural nanocarriers, carrying information molecules from their parent cells and fusing with targeted cells. miRNA-126, specific to endothelial cells and derived from these vesicles, supports vascular integrity and angiogenesis and has protective effects in kidney diseases. OBJECTIVE: This study investigates the delivery of miRNA-126 and anti-miRNA-126 via UC-EVs as natural nanocarriers for treating nephrotoxic injury in vitro. METHOD: The umbilical cord-derived mesenchymal stem cell and UC-EVs were characterized according to specific guidelines. Rat kidney proximal tubular epithelial cells (tubular cells) were exposed to nephrotoxic injury through of gentamicin and simultaneously treated with UC-EVs carrying miRNA-126 or anti-miRNA-126. Specific molecules that manage cell cycle progression, proliferation cell assays, and newly synthesized DNA and DNA damage markers were evaluated. RESULTS: We observed significant increases in the expression of cell cycle markers, including PCNA, p53, and p21, indicating a positive cell cycle regulation with newly synthesized DNA via BrDU. The treatments reduced the expression of DNA damage marker, such as H2Ax, suggesting a lower rate of cellular damage. CONCLUSIONS: The UC-EVs, acting as natural nanocarriers of miRNA-126 and anti-miRNA-126, offer nephroprotective effects in vitro. Additionally, other components in UC-EVs, such as proteins, lipids, and various RNAs, might also contribute to these effects.

Asunto(s)

Vesículas Extracelulares , Células Madre Mesenquimatosas , Cordón Umbilical , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/trasplante , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Animales , Cordón Umbilical/citología , Ratas , Humanos , Proliferación Celular/efectos de los fármacos , MicroARNs/metabolismo , MicroARNs/genética , Ciclo Celular/efectos de los fármacos , Daño del ADN

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STUDY DESIGN: Experimental study utilizing with a standardized model (MASCIS Impactor) of Spinal Cord Injury (SCI) in Balb C mouse model with implantation of mononuclear stem cells derived from the human umbilical cord and placenta blood in the early chronic phase of SCI. OBJECTIVES: The aim of this study was to evaluate the nerve regeneration and motor functional recovery in Balb C mice with surgically induced paraplegia in response to the use of mononuclear stem cells, in early chronic phase (> 2 weeks and < 6 months), because there is yet potential of neuronal and functional recovery as the neuronal scar is not still completely established. METHODS: Forty-eight mice were randomly assigned to 6 groups of 8 animals. Group 1 received the stem cells 3 weeks after the trauma, and Group 2 received them six weeks later. In Group 3, saline solution was injected at the site of the lesion 3 weeks after the trauma, and in Group 4, 6 weeks later. Group 5 underwent only spinal cord injury and Group 6 underwent laminectomy only. The scales used for motor assessment were BMS and MFS for 12 weeks. RESULTS: The intervention groups showed statistically significant motor improvement. In the histopathological analysis, the intervention groups had a lower degree of injury (p < 0.05). Regarding axonal budding, the intervention groups showed increasing in axonal budding in the caudal portion (p < 0.05). CONCLUSIONS: The use of stem cells in mice in the chronic phase after 3 and 6 weeks of SCI brings functional and histopathological benefits to them.

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Modelos Animales de Enfermedad , Ratones Endogámicos BALB C , Regeneración Nerviosa , Placenta , Distribución Aleatoria , Recuperación de la Función , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/fisiopatología , Femenino , Ratones , Humanos , Embarazo , Factores de Tiempo , Regeneración Nerviosa/fisiología , Paraplejía/fisiopatología , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Actividad Motora/fisiología , Cordón Umbilical/citología , Masculino

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Aim: Childhood maltreatment (CM) may affect not only directly exposed individuals but also their offspring. However, the underlying biological mechanisms remain unclear. microRNAs (miRNAs) may play a regulatory role in this process. This study investigates the relationship between maternal exposure to CM and miRNA expression in maternal and perinatal tissues.Methods: We enrolled 43 pregnant women and assessed their CM exposure. We collected maternal blood, cord blood and placental tissue samples during childbirth and performed miRNA profiling using next generation sequencing.Results: Maternal CM was inversely associated with hsa-miR-582-3p levels in cord blood. Pathway analysis revealed that this miRNA regulates genes involved in intrauterine development.Conclusion: Our findings highlight the potential impact of maternal CM exposure on offspring epigenetic mechanisms.

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Child maltreatment (CM) includes physical, sexual and emotional abuse, as well as physical and emotional neglect. CM not only harms those directly exposed but can also negatively impact their offspring. However, the biological reasons behind this are not well understood. To explore this further, our study investigates how CM affects the biology of pregnant women and their newborns through changes in small regulatory molecules called microRNAs (miRNAs). We recruited 43 pregnant women and assessed their exposure to CM. During childbirth, we collected blood samples from the mothers, blood from the umbilical cord and placental samples. We then analyzed the levels of miRNAs in these samples using advanced sequencing technology. We observed that more severe maternal exposure to CM was associated with lower levels of a miRNA named hsa-miR-582-3p in umbilical cord blood. This miRNA regulates genes involved in fetal development in utero and has been linked to spontaneous preterm birth. It may also influence immunologic and stress-related processes. Thus, newborns of mothers who had been exposed to CM may be more vulnerable to adverse effects on their brain development and overall health. Despite our small sample size, our study highlights the importance of addressing CM as an intergenerational concern and provides new insights into the biological mechanisms through which maternal CM can affect offspring.

Asunto(s)

Sangre Fetal , Exposición Materna , MicroARNs , Humanos , Femenino , Sangre Fetal/metabolismo , MicroARNs/genética , MicroARNs/sangre , Embarazo , Adulto , Exposición Materna/efectos adversos , Maltrato a los Niños , Placenta/metabolismo , Epigénesis Genética , Niño

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We describe two cases of umbilical cord (UC) angiomyxoma diagnosed prenatally by sonography in the second trimester of pregnancy. In both cases, a complex mass was detected at the placental insertion site, characterized by an echoic nodule surrounding the umbilical vessels and distal edematous Wharton's jelly. Follow-up scans showed that the mass grew mainly at the expense of its edematous component, with normal uteroplacental Dopplers throughout the remaining of the pregnancy. However, late-onset fetal growth restriction complicated the progress of pregnancy, requiring delivery by Cesarean section at 37 weeks' gestation in both cases. Neonatal courses were unremarkable. An extensive review of the English literature was also performed, collecting 45 similar cases including ours. Our experience as well as the review of the literature confirms that UC angiomyxoma is an uncommon, sporadic condition that is usually detected incidentally during prenatal sonography and presents as an isolated finding. Nevertheless, it represents a high-risk condition for pregnancy complications including prematurity, fetal growth restriction, and fetal demise.

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Mixoma , Ultrasonografía Prenatal , Cordón Umbilical , Humanos , Embarazo , Femenino , Ultrasonografía Prenatal/métodos , Cordón Umbilical/diagnóstico por imagen , Cordón Umbilical/embriología , Adulto , Mixoma/diagnóstico por imagen , Mixoma/embriología

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Containing information molecules from their parent cells and inclining to fuse with targeted cells, bone marrow mesenchymal stromal cells-derived extracellular vesicles (MSCs- EV) are valuable in nanomedicine. BACKGROUND: The effects of aging on the paracrine mechanism and in the production and action of MSCs-EV and their cargos of miR-26a and siRNA-26a for the treatment of tubular renal cells under nephrotoxicity injury remain unelucidated. OBJECTIVE: The purpose of this study was to evaluate MSCs-EV of different ages and their ability to deliver the cargos of miR-26a and siRNA-26a to target renal tubular cells affected by nephrotoxicity injury. METHODS: In a model of gentamicin-induced nephrotoxicity, renal tubular cells treated with MSCs-EV expressing or not expressing microRNA-26a were analyzed. Western blotting was utilized to evaluate cell cycle markers, and MTT assay was utilized to evaluate auto-renovation capacity. RESULTS: Tubular cells under nephrotoxicity injury showed decreased proliferative capacity, but the treatment in the tubular renal cells under nephrotoxicity injury with MSCs-EV expressing microRNA-26a showed nephroprotective effects, regardless of EV age. While the treatment with EV-mediated siRNA-26a failed to preserve the nephroprotective effects equally, regardless of age. CONCLUSION: Mesenchymal stromal cell nanovesicles carry microRNA with nephroprotective proprieties regardless of aging.

Asunto(s)

Proliferación Celular , Túbulos Renales , Células Madre Mesenquimatosas , MicroARNs , Células Madre Mesenquimatosas/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Animales , Túbulos Renales/patología , Túbulos Renales/metabolismo , Envejecimiento/metabolismo , Envejecimiento/patología , Envejecimiento/genética , Gentamicinas/toxicidad , Gentamicinas/efectos adversos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Factores de Edad , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/genética , Línea Celular , Células Cultivadas , Comunicación Paracrina , Modelos Animales de Enfermedad , Humanos

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OBJECTIVE: To identify whether histologically confirmed chorioamnionitis (hCAM) is associated with development of retinopathy of prematurity (ROP). STUDY DESIGN: We retrospectively analyzed 2 different cohorts. Cohort 1 was the national database of newborns in Japan born at ≤1500g or <32 weeks' gestation (January 2003 through April 2021, n = 38 013). Cohort 2 was babies born at <1500g from a single institution in Tsuchiura, Japan, (April 2015 through March 2018, n = 118). RESULTS: For Cohort1, after adjusting for potential confounders, stage III CAM (n = 5554) was associated with lower odds of severe ROP (stage ≥3 or required peripheral retinal ablation) by 14% (OR: 0.86; 95% CI: 0.78-0.94]. CAM of stage I (n = 3277) and II (n = 4319) was not associated with the risk of ROP. For Cohort 2, the odds of severe ROP were significantly reduced in moderate to severe hCAM groups (stage II, OR: 0.06, 95% CI: 0.05-0.82; stage III, OR: 0.10, 95% CI: 0.01-0.84). Neonates with funisitis, comorbidity of hCAM, and a finding of fetal inflammatory response had lower odds of severe ROP (OR: 0.11; 95% CI: 0.01-0.93). CONCLUSIONS: After adjusting for confounders, severe hCAM with fetal inflammatory response was associated with reduced risk of ROP.

Asunto(s)

Corioamnionitis , Retinopatía de la Prematuridad , Humanos , Retinopatía de la Prematuridad/epidemiología , Corioamnionitis/epidemiología , Femenino , Recién Nacido , Estudios Retrospectivos , Embarazo , Masculino , Japón/epidemiología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Recien Nacido Prematuro , Edad Gestacional

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INTRODUCTION: Different factors affect the quality and viability of cord blood stem cells, and therefore the efficacy of umbilical cord stem cell transplantation. Fetal distress is one factor affecting the quantity of CD34+ cells in cord blood. This study was designed to compare the viability and yield of the umbilical cord blood stem cells of women who have undergone emergency lower segment caesarean section for fetal distress or for other causes. MATERIALS AND METHODS: This cross-sectional analytical study was performed at a tertiary care hospital facility with a total sample size of 68: 34 participants had undergone emergency C-section for fetal distress, and 34 had undergone emergency C-section for other causes. Umbilical cord blood was collected ex-utero in a 350 mL bag with citrate-phosphate-dextrose solution with adenine. Three milliliter of blood were transferred to an ethylenediaminetetraacetic acid (EDTA) tube for cell counts and flow cytometry testing for CD34+. The chi-square test was used to compare the total mononuclear cell, CD34+, and viability between the groups. RESULTS: The CD34+ count [mean 4.9 versus 1.1 (× 106 cells/unit)] and total nucleated cell count [mean 14.2 versus 7.5 (× 108/unit)] were significantly higher in cord blood units collected from women who delivered by C-section for fetal distress (p-value <0.05). However, the volume of umbilical cord stem cells and viability of stem cells did not vary significantly based on the presence or absence of fetal distress (p-value >0.05). CONCLUSION: The current study shows that umbilical cord blood collected during fetal distress has a significantly higher content of stem cells and total nucleated cells than the non-fetal distress group.

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Objective: This study aimed to describe the historical experience of a single reference center in Brazil with intrauterine transfusion (IUT) for Rhesus (Rh) alloimmunization, evaluating the major complications and the perinatal outcomes of this procedure. Methods: This retrospective cohort study evaluated data from medical records of pregnant women between 20 and 34 weeks of gestation whose fetuses underwent IUT by cordocentesis between January 1991 and June 2021. The same experienced examiner performed all procedures. Univariate and multivariate logistic regression was used to assess the effect of fetal hydrops, duration of IUT, post-transfusion cord bleeding time, and bradycardia on death (fetal or neonatal). Results: We analyzed data from 388 IUTs in 169 fetuses of alloimmunized pregnant women with a mean age of 29.3 ± 5.1 years. Death and fetal hydrops were significantly associated at first IUT (p < 0.001). We had two cases of emergency cesarean section (mean of 0.51% per IUT) and three cases of premature rupture of the ovular membranes (mean of 0.77% per procedure). Thirty-six deaths were recorded, including 14 intrauterine and 22 neonatal. A higher percentage of neonatal deaths was observed in the group with post-transfusion cord bleeding time > 120 s (45.8%). The odds of neonatal death were 17.6 and 12.9 times higher in cases with hydrops and bradycardia than in cases without hydrops and bradycardia, respectively. The odds of death (fetal and neonatal) were 79.9 and 92.3 times higher in cases with hydrops and bradycardia than in cases without hydrops and bradycardia, respectively. Conclusions: The most common complications of IUT for Rh alloimmunization were post-transfusion cord bleeding, fetal bradycardia, premature rupture of ovular membranes, and emergency cesarean section. The IUT complication most associated with death (fetal and neonatal) was bradycardia, and the perinatal outcomes were worse in fetuses with hydrops.

RESUMEN

BACKGROUND: Exposure to toxins during pregnancy is the main modifiable behavior that affects the placenta and, consequently, the fetus. In particular, smoking is a recognized risk factor for negative outcomes. Our study pretended to examine gross and microscopic placental features in women who reported exposure to tobacco, alcohol, or other psychoactive substances. METHODS: In this observational case-control study, we collected 706 placentas to assess precise substance exposure histological-interaction features of in the placenta. We examined gross and microscopic placental features, and then recorded maternal and newborn clinical conditions. RESULTS: We found that 4.8% of mothers admitted to consumption of some type of (harmful) substance. The most common pre-existing maternal condition was obesity (20.3%); predominant complications included amniotic infection (32.3%), urinary tract infection (14.5%) and hypertensive disorders of pregnancy (14.5%). In newborns, we discovered positive associations as respiratory distress syndrome. Macroscopically, exposed mothers had heavier placentas, more true knots, and single umbilical artery; microscopically, they were more likely to exhibit fetal vascular malperfusion (FVM). CONCLUSIONS: Until our present study, no research linked umbilical cord defects to toxic substance exposure; our study results do confirm association with adverse outcomes in neonates and alterations in the neuro-cardio-placental circuit through FVM. IMPLICATIONS: The results are confirming the importance of this modifiable risk factor and how its presence may potentially affect the course of pregnancy, as well as the health of both mother and child.

Asunto(s)

Placenta , Complicaciones del Embarazo , Trastornos Relacionados con Sustancias , Humanos , Femenino , Embarazo , Placenta/patología , Recién Nacido , Estudios de Casos y Controles , Adulto , Complicaciones del Embarazo/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/complicaciones , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Fumar/efectos adversos , Fumar/epidemiología , Factores de Riesgo

RESUMEN

Wound healing after skin injury is a complex process, particularly in equines where leg wounds are prevalent and their repair is complicated due to the anatomical characteristics. Conventional treatments are not effective enough. The umbilical cord offers an unlimited source of adult mesenchymal stem cells (ucMSCs) from Wharton's jelly tissue. The present study aims to demonstrate the safety and therapeutic potential of the allogeneic use of equine ucMSCs (e-ucMSCs) in the healing of severe equine leg wounds. The methods employed were the isolation, culture and expansion of e-ucMSCs. Flow cytometry and a PCR assay were used for cell characterization. This study included an immunomodulation assay, a murine pre-clinical trial and the first phase of an equine clinical trial. Our results showed that e-ucMSCs express a functional HLA-G homolog, EQMHCB2. In the immunomodulation assay, the e-ucMSCs inhibited the proliferation of activated equine peripheral blood mononuclear cells (e-PBMCs). In the murine pre-clinical trial, e-ucMSCs reduced healing time by 50%. In the equine clinical trial, the injection of e-ucMSCs into severe leg lesions improved the closure time and quality of the tissues involved, regenerating them without fibrous tissue scar formation. In conclusion, the results of this study suggest that e-ucMSCs can be used allogeneically for wound healing by creating a tolerogenic environment.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Células Madre Mesenquimatosas , Animales , Caballos , Ratones , Leucocitos Mononucleares , Cordón Umbilical , Cicatriz

RESUMEN

Induced pluripotent stem cells (iPSCs) are reprogrammed cells with a remarkable capacity for unlimited expansion and differentiation into various cell types. Companies worldwide are actively engaged in developing clinical-grade iPSC lines to address the needs of regenerative medicine, immunotherapies, and precision medicine. However, ensuring the safety and quality of iPSCs is essential, with adherence to Good Manufacturing Practices (GMP) and ethical considerations being paramount. Perinatal cell and tissue banks, such as umbilical cord (UC) blood and tissue banks, are emerging as ideal sources for generating iPSCs due to their unique characteristics and GMP compliance. These banks provide access to immature cells with limited environmental exposure, known family and medical histories of donors, and readily available resources, thereby reducing the time and cost associated with personalized treatment strategies. This study describes the establishment of the first clinical-grade iPSC lines from umbilical cord mesenchymal stromal cells in Brazil. The process involved rigorous quality control measures, safety assessments, and adherence to regulatory standards, resulting in iPSCs with the necessary characteristics for clinical use, including sterility, genomic integrity, and stability. Importantly, the study contributes to the development of a Current Good Manufacturing Practice-compliant iPSC production pipeline in Brazil, using commercially available, chemically defined, and xeno-free products, along with validation by national outsourced laboratories, thereby facilitating the adoption of this technology within the country. The study emphasizes Brazil's contribution to the progress of translational medicine and the promotion of scientific advancements within the field of regenerative and precision medicine.

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Células Madre Pluripotentes Inducidas , Células Madre Mesenquimatosas , Cordón Umbilical , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Cordón Umbilical/citología , Diferenciación Celular , Línea Celular , Técnicas de Cultivo de Célula/métodos , Brasil , Medicina Regenerativa/métodos

RESUMEN

Osteoarthritis (OA) is the most common degenerative joint disease. Mesenchymal stromal cells (MSC) are promising cell-based therapy for OA. However, there is still a need for additional randomized, dose-dependent studies to determine the optimal dose and tissue source of MSC for improved clinical outcomes. Here, we performed a dose-dependant evaluation of umbilical cord (UC)-derived MSC (Celllistem) in a murine model and in knee OA patients. For the preclinical study, a classical dose (200.000 cells) and a lower dose (50.000 cells) of Cellistem were intra-articularly injected into the mice knee joints. The results showed a dose efficacy response effect of Cellistem associated with a decreased inflammatory and degenerative response according to the Pritzker OARSI score. Following the same approach, the dose-escalation phase I clinical trial design included 3 sequential cohorts: low-dose group (2 × 106 cells), medium-dose group (20 × 106), and high-dose group (80 × 106). All the doses were safe, and no serious adverse events were reported. Nonetheless, 100% of the patients injected with the high-dose experienced injection-related swelling in the knee joint. According to WOMAC total outcomes, patients treated with all doses reported significant improvements in pain and function compared with baseline after 3 and 6 months. However, the improvements were higher in patients treated with both medium and low dose as compared to high dose. Therefore, our data demonstrate that the intra-articular injection of different doses of Cellistem is both safe and efficient, making it an interesting therapeutic alternative to treat mild and symptomatic knee OA patients. Trial registration ClinicalTrials.gov NCT03810521.

Asunto(s)

Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Osteoartritis de la Rodilla , Animales , Humanos , Ratones , Inyecciones Intraarticulares , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Trasplante de Células Madre Mesenquimatosas/métodos , Osteoartritis de la Rodilla/terapia , Resultado del Tratamiento , Cordón Umbilical

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PURPOSE: The velamentous cord insertion is a rare pathology in which the umbilical blood vessels branch before reaching the placenta; by varying its structure, the cord becomes prone to spontaneous internal ruptures. This pathology is an obstetric emergency, so its early diagnosis is essential. METHODS AND RESULTS: We present a 27-year-old pregnant woman who attends an antenatal check-up for a routine third-trimester examination. Ultrasound reveals grade I polyhydramnios and suggestive findings of a trivascular umbilical cord with velamentous insertion 35 mm from the nearest placental border. The ultrasound diagnosis allowed a term delivery by elective cesarean section, avoiding severe complications of the maternal-fetal binomial. CONCLUSION: Velamentous cord insertion can and should have an early prenatal diagnosis, even from the second trimester, through imaging techniques such as transabdominal ultrasound or color Doppler. Early detection and appropriate peripartum management will highly reduce complications during labor.

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Cesárea , Enfermedades Vasculares , Embarazo , Femenino , Humanos , Adulto , Placenta/diagnóstico por imagen , Diagnóstico Prenatal , Ultrasonografía , Ultrasonografía Prenatal

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ABSTRACT Objective: To assess the effects of cobalt chloride (CoCl2) as a hypoxia mimicking agent on human umbilical cord mesenchymal stem cells (hUCMSCs) expression of HIF-1α and mTOR for use in regenerative dentistry. Material and Methods: Human umbilical cord mesenchymal stem cells were isolated and then cultured. The characteristics of stemness were screened and confirmed by flow cytometry. The experiment was conducted on hypoxia (H) and normoxia (N) groups. Each group was divided and incubated into 24-, 48-, and 72-hours observations. Hypoxic treatment was performed using 100 µM CoCl2 on 5th passage cells in a conventional incubator (37°C; 5CO2). Then, immunofluorescence of HIF-1α and mTOR was done. Data was analyzed statistically using One-way ANOVA and Tukey's HSD. Results: Significant differences were found between normoxic and hypoxic groups on HIF-1α (p=0.015) and mTOR (p=0.000) expressions. The highest HIF-1α expression was found at 48 hours in the hypoxia group, while for mTOR at 24 hours in the hypoxia group. Conclusion: Hypoxia using cobalt chloride was able to increase human umbilical cord mesenchymal stem cells expression of HIF-1α and mTOR.

Asunto(s)

Humanos , Cordón Umbilical/citología , Cloruros/química , Cobalto/química , Células Madre Mesenquimatosas/citología , Hipoxia/patología , Análisis de Varianza , Citometría de Flujo

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SUMMARY OBJECTIVE: Placenta accreta spectrum (PAS) is defined as the attachment of the placenta to the uterine wall in varying degrees. However, the studies have explored that the underlying molecular mechanisms of the PAS are very limited. Sirtuins 1 (SIRT1) is associated with placental development by controlling trophoblast cell invasion and remodeling of spiral arteries. We aimed to determine the expression level of SIRT1 in placentas, and maternal and umbilical cord serum of patients with PAS. METHODS: In total, 30 individuals in control, 20 patients in the placenta previa group, and 30 patients in the PAS group were included in this study. The expression levels of SIRT1 in the placentas were determined by Western blot and immunohistochemistry. Serum levels of SIRT1 in maternal and umbilical cord blood were determined by ELISA. RESULTS: SIRT1 was significantly lower in placentas of the PAS. However, maternal and umbilical cord serum samples were not significantly different between groups. CONCLUSION: SIRT1 may play an important role in the pathogenesis of the PAS.

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ABSTRACT Introduction and hypothesis: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for allogeneic hematopoietic stem cell transplantation in the absence of a compatible donor. The UCB transplantation has a lower incidence of chronic graft versus host disease (GvHD), but is associated with slower engraftment and slower immune reconstitution, compared to other sources. Dendritic cells (DCs) and Natural Killer cells (NKs) play a central role in the development of GvHD and the graft versus leukemia (GvL) effect, as well as in the control of infectious complications. Method: We quantified by multiparametric flow cytometry monocytes, lymphocytes, NK cells, and DCs, including their subsets, in UCB samples from 54 healthy newborns and peripheral blood (PB) from 25 healthy adult volunteers. Results: In the UCB samples, there were higher counts of NK cells 56bright16- (median 0.024 × 109/L), compared to the PB samples (0.012 × 109/L, p < 0.0001), NK 56dim16bright (median 0.446 × 109/L vs. 0.259 × 109/L for PB samples, p = 0.001) and plasmacytoid dendritic cells (pDCs, median 0.008 × 109/L for UCB samples vs. 0.006 × 109/L for PB samples, p = 0.03). Moreover, non-classic monocyte counts were lower in UCB than in PB (median 0.024 × 109/L vs. 0.051 × 109/L, respectively, p < 0.0001). Conclusion: In conclusion, there were higher counts of NK cells and pDCs and lower counts of non-classic monocytes in UCB than in PB from healthy individuals. These findings might explain the lower incidence and severity of chronic GvHD, although maintaining the GvL effect, in UCB transplant recipients, compared to other stem cell sources.

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Sangre Fetal

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Umbilical cord blood (UCB) serves as a source of hematopoietic stem and progenitor cells (HSPCs) utilized in the regeneration of hematopoietic and immune systems, forming a crucial part of the treatment for various benign and malignant hematological diseases. UCB has been utilized as an alternative HSPC source to bone marrow (BM). Although the use of UCB has extended transplantation access to many individuals, it still encounters significant challenges in selecting a histocompatible UCB unit with an adequate cell dose for a substantial proportion of adults with malignant hematological diseases. Consequently, recent research has focused on developing ex vivo expansion strategies for UCB HSPCs. Our results demonstrate that co-cultures with the investigated mesenchymal stromal cells (MSCs) enable a 10- to 15-fold increase in the cellular dose of UCB HSPCs while partially regulating the proliferation capacity when compared to HSPCs expanded with early acting cytokines. Furthermore, the secretory profile of UCB-derived MSCs closely resembles that of BM-derived MSCs. Moreover, both co-cultures exhibit alterations in cytokine secretion, which could potentially impact HSPC proliferation during the expansion process. This study underscores the fact that UCB-derived MSCs possess a remarkably similar supportive capacity to BM-derived MSCs, implying their potential use as feeder layers in the ex vivo expansion process of HSPCs.

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Enfermedades Hematológicas , Trasplante de Células Madre Hematopoyéticas , Células Madre Mesenquimatosas , Embarazo , Femenino , Adulto , Humanos , Antígenos CD34 , Sangre Fetal , Células Madre Hematopoyéticas , Técnicas de Cocultivo , Trasplante de Células Madre Hematopoyéticas/métodos , Proliferación Celular

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BACKGROUND: Acute fetal distress (AFD) is a condition that requires timely diagnosis because it generates hypoxia, acidosis, and even intrauterine death. This study aimed to determine lactate and pH values in the umbilical cord in full-term newborns (NBs) with a history of AFD. METHODS: We conducted a cross-sectional study in full-term NBs of mothers with at least one perinatal, neonatal, or gasometric AFD antecedent. Neonatal morbidity was considered: if 1-min Apgar ≤ 6, or advanced neonatal maneuvers, or neonatal intensive care unit (NICU) admissions were necessary. The cutoff points were lactate > 4mmol/L and pH < 7.2. RESULTS: Of 66 NBs, 33.3% of mothers presented at least one antecedent for developing AFD; 22.7% presented hypertensive pregnancy disease, 13.6% oligohydramnios, and 63.6% other factors. Perinatally, 28.7% required advanced neonatal resuscitation maneuvers and 7.5% admission to the NICU. In the gasometry, the lactate and pH values for the neonatal morbidity of the NBs' group were 4.726 ± 1.401 and 7.293 ± 0.056, respectively, versus 2.240 ± 0.318 and 7.359 ± 0.022 (p < 0.05) for the group without associated neonatal morbidity. CONCLUSIONS: Lactate values in the umbilical cord increased by 25%, and pH decreased by one percent in NBs with a history of AFD and associated morbidity.

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INTRODUCCIÓN: El sufrimiento fetal agudo (SFA) es una condición que amerita un diagnóstico oportuno debido a que genera hipoxia, acidosis e incluso la muerte intrauterina. El objetivo de este estudio fue determinar los valores de lactato y pH en cordón umbilical en recién nacidos de término con antecedente SFA. MÉTODOS: Se llevó a cabo un estudio transversal, en recién nacidos a término, de madres que tuvieron al menos un antecedente para SFA de tipo perinatal, neonatal o gasométrico. Se consideró morbilidad neonatal cuando presentaron Apgar al minuto ≤ 6, o requirieron maniobras avanzadas de reanimación neonatal, o ingreso a Unidad de Cuidados Intensivos Neonatales (UCIN). El punto de corte fue > 4 mmol/L para los valores de lactato y pH < 7.2. RESULTADOS: De un total de 66 recién nacidos, el 33.3% de las madres presentaron al menos un antecedente para desarrollar SFA; el 22.7% presentó enfermedad hipertensiva del embarazo, el 13.6%, oligohidramnios, y el 63.6%, otros factores. El 28.7% requirieron maniobras avanzadas de la reanimación neonatal y el 7.5%, el ingreso a la UCIN. En la gasometría, el valor de lactato y pH para el grupo de recién nacidos con morbilidad neonatal fue de 4.726 ± 1.401 y 7.293 ± 0.056 respectivamente, versus 2.240 ± 0.318 y 7.359 ± 0.022 (p < 0.05) para el grupo sin morbilidad neonatal asociada. CONCLUSIONES: Se observó un incremento del 25% de los valores de lactato en cordón umbilical y una disminución del 1% del pH en los recién nacidos con antecedente de SFA y morbilidad asociada.

Asunto(s)

Hipertensión , Ácido Láctico , Femenino , Embarazo , Recién Nacido , Humanos , Estudios Transversales , Sufrimiento Fetal/diagnóstico , Resucitación , Concentración de Iones de Hidrógeno

RESUMEN

La insuficiencia de vitamina D (VD) en el embarazo se relaciona con una mayor incidencia de cesáreas, preeclampsia y partos prematuros. Objetivo: evaluar si el grado de insuficiencia de VD se asocia a mayor número de cesáreas y evaluar la correlación entre la 25 hidroxivitamina D (25OHD) materna y en sangre del cordón del recién nacido. Las mujeres (n=127) se dividieron según sus niveles de 25OHD (ng/mL):G1:<20 (deficiencia), G2:20-30 (insuficiencia), G3:>30 (suficiencia). Se registraron edad; edad gestacional (EG); índice de masa corporal (IMC); tensión arterial sistólica y diastólica; tipo de parto y la estación del año en que se tomó la muestra. Se determinaron calcemia (ng/mL); 25OHD; parathormona intacta (pg/mL); fosfatasa alcalina ósea (UI/L) y crosslaps (pg/mL). La edad media fue de 26±6 años y la EG de 35,8±2,7 semanas, sin diferencias entre grupos. El porcentaje de cesáreas fue mayor en G1 que en G2 y G3 (31,3%, 21,4% y 25%, respectivamente; p<0,05). El mayor porcentaje de muestras se tomó en primavera (p<0,05). No se observaron diferencias en las demás variables maternas estudiadas. La 25OHD materna correlacionó positivamente con los valores de la sangre de cordón de sus respectivos recién nacidos (r= 0,67; p<0,0001). Independientemente de la época del año y del IMC, se observó que un porcentaje significativo de las mujeres embarazadas estudiadas tenía niveles de 25OHD inferiores a 30 ng/mL. Conclusión: evidenciamos que la deficiencia de VD materna se asoció al número de cesáreas. Asimismo, los niveles séricos de 25OHD en sangre de cordón umbilical correlacionaron significativamente con los maternos. (AU)

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Vitamin D (VD) insufficiency in pregnancy is associated with a higher incidence of cesarean section, preeclampsia, and preterm delivery. Objective: to evaluate if the degree of VD insufficiency is associated with the incidence of cesarean section and to determine the correlation between maternal and newborn cord blood 25-hydroxy VS (25OHD). Women (n=127) were divided according to their 25OHD levels (ng/mL): G1:<20 (deficiency), G2:20-30 (insufficiency), G3:>30 (sufficiency). Age; gestational age (GA); body mass index (BMI); systolic and diastolic blood pressure (mmHg); type of delivery and the season of the year in which the sample was taken were recorded. Calcemia (ng/mL); 25OHD; intact parathormone (pg/mL); bone alkaline phosphatase (IU/L) and Crosslaps (pg/mL) levels were determined. Mean age was 26±6 years and GA was 35.8±2.7 weeks with no differences among groups. The % of cesarean sections was higher in G1 than in G2 and G3 (31.3%, 21.4% and 25%; p<0.05). The highest % of samples were taken in spring (p<0.05). No differences were observed in the other maternal variables studied. Maternal serum 25OHD levels correlated positively with those of cord blood from their respective newborns (r=0.67; p<0.0001). Regardless the season of the year and BMI, a high % of the studied pregnant women presented 25OHD levels lower than 30 ng/ml. Conclusion: we found that maternal VD deficiency is associated with the number of cesarean sections. In addition, 25OHD levels in the newborn significantly correlate with maternal serum levels. (AU)

Asunto(s)

Humanos , Femenino , Embarazo , Adulto , Adulto Joven , Deficiencia de Vitamina D/complicaciones , Embarazo/estadística & datos numéricos , Cesárea/estadística & datos numéricos , Tercer Trimestre del Embarazo , Estaciones del Año , Vitamina D , Calcio de la Dieta/administración & dosificación , 25-Hidroxivitamina D 2/sangre , Incidencia , Edad Gestacional , Sangre Fetal , Trabajo de Parto Prematuro/epidemiología

Asunto(s)

Distocia , Enfermedades de los Caballos , Embarazo , Femenino , Animales , Caballos , Distocia/veterinaria , Feto , Enfermedades de los Caballos/diagnóstico , Enfermedades de los Caballos/etiología