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Stem Cells Translational Medicine Oct 2023Neonatal cell therapy applications are increasing; however, data on allogeneic cell therapy are limited.
BACKGROUND
Neonatal cell therapy applications are increasing; however, data on allogeneic cell therapy are limited.
OBJECTIVE
To summarize evidence on allogeneic cell therapy in term and preterm neonates.
METHODS
Cochrane Central Register of Controlled Trials, Embase, Ovid Medline, and various registries were searched for studies investigating the safety, feasibility, and efficacy of allogeneic cell therapy in neonates. Two authors independently selected the articles, extracted data, and assessed the risk of bias.
RESULTS
Twelve published (153 infants) and 21 ongoing studies were included. These studies predominantly sourced allogeneic cells from umbilical cord blood (UCB). Mesenchymal stromal cells (MSCs) were the main cell type used (134 of 153 infants); others included UCB-derived total nucleated cells (TNCs) and human amnion epithelial cells (hAECs). Applications included bronchopulmonary dysplasia (BPD; 113 infants), Krabbe disease (13 infants), intraventricular haemorrhage (10 infants), perinatal arterial ischemic stroke (10 infants), hypoxic-ischaemic encephalopathy (6 infants), and necrotizing enterocolitis (1 infant). Nine out of 12 studies did not report any serious adverse events (SAEs) related to cell administration. Three studies reported SAEs, such as graft versus host disease (GVHD) in 5 infants (UCB-derived TNCs for Krabbe disease); and transient cardiorespiratory compromise in 1 infant (hAECs for BPD). Data on efficacy outcomes were limited.
CONCLUSION
The safety and feasibility of allogeneic cell therapy applications in neonates are available, mainly from the use of MSCs. Further safety data for other cell types are required, and the risk of GVHD in different settings needs to be determined. Efficacy studies are largely lacking for all cell types.
PROTOCOL REGISTRATION
The protocol was registered with PROSPERO (registration number CRD42023397876), the international prospective register for systematic reviews (https://www.crd.york.ac.uk/PROSPERO).
PubMed: 37603845
DOI: 10.1093/stcltm/szad048 -
BMC Pregnancy and Childbirth Sep 2023Prelabour rupture of membranes at term affects approximately 10% of women during pregnancy, and it is often associated with a higher risk of infection than when the...
INTRODUCTION
Prelabour rupture of membranes at term affects approximately 10% of women during pregnancy, and it is often associated with a higher risk of infection than when the membranes are intact. In an attempt to control the risk of infection, two main approaches have been used most widely in clinical practice: induction of labour (IOL) soon after the rupture of membranes, also called active management (AM), and watchful waiting for the spontaneous onset of labour, also called expectant management (EM). In addition, previous studies have demonstrated that vaginal examinations increase the risk of chorioamnionitis. However, the effect of vaginal examinations in the context of prelabour rupture of membranes have not been researched to the same extent.
METHODS
This systematic review analyses and critiques the latest research on the management of term prelabour rupture of membranes, including the effect of vaginal examinations during labour, with a focus on the outcomes of both normal birth, and chorioamnionitis. Due to its complexity, three research questions were identified using the PICO diagram, and subsequently, the results from these searches were combined. The systematic review aimed to identify randomised controlled trials (RCTs) and observational studies that compared active vs expectant management, included number of vaginal examinations and had chorioamnionitis and/or normal birth as outcomes. The following databases were used: MEDLINE, EMBASE, Maternity and Infant care, LILACS, CINAHL and the Cochrane Central Register of Controlled trials. Quality was assessed using a tool developed especifically for this study that included questions from CASP and the Cochrane risk of bias tool. Due to the high degree of heterogeneity meta-analysis was not deemed appropriate. Therefore, simple narrative analysis was carried out.
RESULTS
Thirty-two studies met the inclusion criteria, of which 27 were RCTs and 5 observational studies. The overall quality of the studies wasn't high, 15 out of the 32 studies were deemed to be low quality and only 17 out of 32 studies were deemed to be of intermediate quality. The systematic review revealed that the management of term prelabour rupture of membranes continues to be controversial. Previous research has compared active management (Induction of labour shortly after the rupture of membrane) against expectant management (watchful waiting for the spontaneous onset of labour). Although previous studies have demonstrated that vaginal examinations increase the risk of chorioamnionitis, no prospective studies have included an intervention to reduce the number of vaginal examinations.
CONCLUSION
A RCT assessing the consequences of active management and expectant management as well as the effect of vaginal examinations during labour for term prelabour rupture of membranes is necessary.
Topics: Female; Pregnancy; Infant; Child; Humans; Chorioamnionitis; Delivery, Obstetric; Labor, Obstetric; Databases, Factual; Infant Care
PubMed: 37684576
DOI: 10.1186/s12884-023-05878-x -
JAMA Oct 2023
Topics: Female; Humans; Pregnancy; Amnion; Infusions, Parenteral; Obstetric Surgical Procedures; Pregnancy Outcome; Prenatal Care
PubMed: 37847278
DOI: 10.1001/jama.2023.15927 -
The Journal of Maternal-fetal &... Dec 2023Early-onset neonatal sepsis (EONS) remains an important cause of neonatal mortality and has many risk factors, therefore, this study aimed to investigate the perinatal... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Early-onset neonatal sepsis (EONS) remains an important cause of neonatal mortality and has many risk factors, therefore, this study aimed to investigate the perinatal risk factors for EONS.
METHODS
We searched CNKI, Wan Fang, VIP, CBM, PubMed, Embase, and Web of Science to compile studies regarding the incidence of neonatal early-onset sepsis, published up to 1 May 2022. To evaluate the quality of the included studies, we used the Newcastle-Ottawa Scale, and the RevMan5.3 software was used for meta-analysis.
RESULTS
A total of 17 studies were included, with 1987 cases in the case group and 4814 cases in the control group. Meta-analysis showed that perinatal asphyxia or intrauterine distress (OR = 3.00, 95% CI: 2.18-4.13), amniotic fluid meconium contamination (OR = 4.51, 95% CI: 2.31-8.81), group B streptococcal (GBS) colonization in pregnant women (OR = 2.13, 95% CI: 1.48-3.05), chorioamnionitis (OR = 4.58, 95% CI: 2.61-8.05), premature rupture of membranes (OR = 2.63, 95% CI: 2.09-3.30), lower gestational age (OR = 1.31, 95% CI: 1.18-1.44), maternal urinary or reproductive tract infection (OR = 3.61, 95% CI: 2.14-6.11), perinatal fever (OR = 3.59, 95% CI: 2.25-5.71), very low birth weight (OR = 3.79, 95% CI: 2.14-6.73), and vaginal examination ≥3 times (OR = 7.95, 95% CI: 4.04-15.64) were the perinatal risk factors for EONS.
CONCLUSION
Perinatal asphyxia or intrauterine distress, meconium contamination in amniotic fluid, GBS colonization in pregnant women, chorioamnionitis, premature rupture of membranes, lower gestational age, maternal urinary tract or reproductive tract infection, perinatal fever, very low birth weight, and vaginal examinations ≥3 times may increase the risk of EONS.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Neonatal Sepsis; Asphyxia; Chorioamnionitis; Reproductive Tract Infections; Amniotic Fluid; Fever; Premature Birth
PubMed: 37743349
DOI: 10.1080/14767058.2023.2259049 -
Journal of Functional Biomaterials Aug 2023Partial or complete dentures are constructed from thermoplastic resins that are thermally processed and molded. This review examines the presently available evidence for... (Review)
Review
Partial or complete dentures are constructed from thermoplastic resins that are thermally processed and molded. This review examines the presently available evidence for the cytotoxicity of thermoplasticized denture base resins on human gingival epithelial cells, adipose cells, and fibroblasts; human amnion fibroblasts; and mouse fibroblasts. Electronic searches were performed on PubMed, Scopus, Web of Science, and Google Scholar databases to identify relevant articles to be included in the review until September 2022. Clinical, in vivo, and in vitro studies in English language were searched for. The quality of the studies was assessed using the Toxicological data Reliability Assessment tool (ToxRTool) developed by the European Commission's Joint Research Centre. GRADE assessment was used to evaluate the certainty of evidence. Seven in vitro studies were included in the review. The overall risk of bias was determined to be high, with the majority of studies assessed found to be reliable with restrictions or not reliable. Only two studies were considered reliable without restrictions based on ToxRTool assessment. The effect of thermoplastic denture base resins on viability and cell adherence of human gingival or amnion fibroblasts and mouse fibroblasts (L929s) is not significant. Conditioned media from unpolished specimens of resins were significantly more toxic to cultured cells than those from polished specimens. This may be of concern in cases of poor post-processing of dentures. Based on the limited evidence available, there is low-certainty evidence that thermoplastic denture base resins appear to be biocompatible and show insignificant cytotoxicity. Further well-designed trials adhering to standard reporting guidelines and using objective measures are necessary before outlining universal guidelines for best practice. Long-term in vivo and clinical assessment is necessary to corroborate laboratory findings with clinical outcomes. Denture base resins are in constant contact with oral tissues, and cytotoxic components released by the resins may irritate or inflame the tissues or provoke an allergic response.
PubMed: 37623656
DOI: 10.3390/jfb14080411 -
Archives of Gynecology and Obstetrics Mar 2024Magnesium sulfate (MgSO) has been widely used in obstetrics as a mean to help decrease maternal and neonatal morbidity in various antenatal pathology. As a factor, it... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Magnesium sulfate (MgSO) has been widely used in obstetrics as a mean to help decrease maternal and neonatal morbidity in various antenatal pathology. As a factor, it seems to regulate immunity and can, thus, predispose to infectious morbidity. To date, it remains unknown if its administration can increase the risk of chorioamnionitis. In the present meta-analysis, we sought to accumulate the available evidence.
METHODS
We systematically searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, and Google Scholar databases in our primary search along with the reference lists of electronically retrieved full-text papers.
RESULTS
Eight studies were included that investigated the incidence of chorioamnionitis among parturient that received MgSO and control patients. Magnesium sulfate was administered in 3229 women and 3330 women served as controls as they did not receive MgSO. The meta-analysis of data revealed that there was no association between the administration of magnesium sulfate and the incidence of chorioamnionitis (OR 0.98, 95% CI 0.73, 1.32). Rucker's analysis revealed that small studies did not significantly influence the statistical significance of this finding (OR 1.12, 95% CI 0.82, 1.53). Trial sequential analysis revealed that the required number to safely interpret the primary outcome was not reached. Two studies evaluated the impact of MgSO in neonates delivered in the setting of chorioamnionitis. Neither of these indicated the presence of a beneficial effect in neonatal morbidity, including the risk of cerebral palsy, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, stillbirth, or neonatal death.
CONCLUSION
Current evidence indicates that magnesium sulfate is not associated with an increased risk of maternal chorioamnionitis. However, it should be noted that its effect on neonatal outcomes of offspring born in the setting of chorioamnionitis might be subtle if any, although the available evidence is very limited.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Chorioamnionitis; Magnesium Sulfate; Stillbirth; Fetal Diseases; Perinatal Death
PubMed: 37768342
DOI: 10.1007/s00404-023-07221-3 -
Frontiers in Pediatrics 2023The role of circulating fetal monocytes in bronchopulmonary dysplasia is not known. We utilized a humanized mouse model that supports human progenitor cell engraftment...
RATIONALE
The role of circulating fetal monocytes in bronchopulmonary dysplasia is not known. We utilized a humanized mouse model that supports human progenitor cell engraftment (MISTRG) to test the hypothesis that prenatal monocyte programming alters early lung development and response to hyperoxia.
METHODS
Cord blood-derived monocytes from 10 human infants were adoptively transferred into newborn MISTRG mice at p0 (1 × 10 cells/mouse, intrahepatic injection) followed by normoxia versus hyperoxia (85% oxygen × 14 days). Lungs were harvested at p14 for alveolar histology (alveolar count, perimeter and area) and vascular parameters (vWF staining for microvessel density, Fulton's index). Human CD45 staining was conducted to compare presence of hematopoietic cells. Murine lung parameters were compared among placebo and monocyte-injected groups. The individual profiles of the 10 patients were further considered, including gestational age (GA; = 2 term, = 3 moderate/late preterm, and = 5 very preterm infants) and preeclampsia ( = 4 patients). To explore the monocyte microenvironment of these patients, 30 cytokines/chemokines were measured in corresponding human plasma by multiplex immunoassay.
RESULTS
Across the majority of patients and corresponding mice, MISTRG alveolarization was simplified and microvessel density was decreased following hyperoxia. Hyperoxia-induced changes were seen in both placebo (PBS) and monocyte-injected mice. Under normoxic conditions, alveolar development was altered modestly by monocytes as compared with placebo ( < 0.05). Monocyte injection was associated with increased microvessel density at P14 as compared with placebo (26.7 ± 0.73 vs. 18.8 ± 1.7 vessels per lung field; < 0.001). Pooled analysis of patients revealed that injection of monocytes from births complicated by lower GA and preeclampsia was associated with changes in alveolarization and vascularization under normoxic conditions. These differences were modified by hyperoxia. CD45+ cell count was positively correlated with plasma monocyte chemoattractant protein-1 ( < 0.001) and macrophage inflammatory protein-1β ( < 0.01). Immunohistochemical staining for human CD206 and mouse F4/80 confirmed absence of macrophages in MISTRG lungs at P14.
CONCLUSIONS
Despite the inherent absence of macrophages in early stages of lung development, immunodeficient MISTRG mice revealed changes in alveolar and microvascular development induced by human monocytes. MISTRG mice exposed to neonatal hyperoxia may serve as a novel model to study isolated effects of human monocytes on alveolar and pulmonary vascular development.
PubMed: 37520051
DOI: 10.3389/fped.2023.1146014 -
Cells Aug 2023The liver is a vital organ responsible for metabolic and digestive functions, protein synthesis, detoxification, and numerous other necessary functions. Various acute,... (Review)
Review
The liver is a vital organ responsible for metabolic and digestive functions, protein synthesis, detoxification, and numerous other necessary functions. Various acute, chronic, and neoplastic disorders affect the liver and hamper its biological functions. Most of the untreated liver diseases lead to inflammation and fibrosis which develop into cirrhosis. The human amniotic membrane (hAM), the innermost layer of the fetal placenta, is composed of multiple layers that include growth-factor rich basement membrane, epithelial and mesenchymal stromal cell layers. hAM possesses distinct beneficial anti-fibrotic, anti-inflammatory and pro-regenerative properties via the secretion of multiple potent trophic factors and/or direct differentiation into hepatic cells which place hAM-based therapies as potential therapeutic strategies for the treatment of chronic liver diseases. Decellularized hAM is also an ideal scaffold for liver tissue engineering as this biocompatible niche provides an excellent milieu for cell proliferation and hepatocytic differentiation. Therefore, the current review discusses the therapeutic potential of hAM and its derivatives in providing therapeutic solutions for liver pathologies including acute liver failure, metabolic disorders, liver fibrosis as well as its application in liver tissue engineering.
Topics: Humans; Female; Pregnancy; Amnion; Liver Diseases; Liver Cirrhosis; Hepatocytes
PubMed: 37626924
DOI: 10.3390/cells12162114 -
Frontiers in Physiology 2023Novel therapeutics are emerging to mitigate damage from perinatal brain injury (PBI). Few newborns with PBI suffer from a singular etiology. Most experience cumulative...
Novel therapeutics are emerging to mitigate damage from perinatal brain injury (PBI). Few newborns with PBI suffer from a singular etiology. Most experience cumulative insults from prenatal inflammation, genetic and epigenetic vulnerability, toxins (opioids, other drug exposures, environmental exposure), hypoxia-ischemia, and postnatal stressors such as sepsis and seizures. Accordingly, tailoring of emerging therapeutic regimens with endogenous repair or neuro-immunomodulatory agents for individuals requires a more precise understanding of ligand, receptor-, and non-receptor-mediated regulation of essential developmental hormones. Given the recent clinical focus on neurorepair for PBI, we hypothesized that there would be injury-induced changes in erythropoietin (EPO), erythropoietin receptor (EPOR), melatonin receptor (MLTR), NAD-dependent deacetylase sirtuin-1 (SIRT1) signaling, and hypoxia inducible factors (HIF1α, HIF2α). Specifically, we predicted that EPO, EPOR, MLTR1, SIRT1, HIF1α and HIF2α alterations after chorioamnionitis (CHORIO) would reflect relative changes observed in human preterm infants. Similarly, we expected unique developmental regulation after injury that would reveal potential clues to mechanisms and timing of inflammatory and oxidative injury after CHORIO that could inform future therapeutic development to treat PBI. To induce CHORIO, a laparotomy was performed on embryonic day 18 (E18) in rats with transient uterine artery occlusion plus intra-amniotic injection of lipopolysaccharide (LPS). Placentae and fetal brains were collected at 24 h. Brains were also collected on postnatal day 2 (P2), P7, and P21. EPO, EPOR, MLTR1, SIRT1, HIF1α and HIF2α levels were quantified using a clinical electrochemiluminescent biomarker platform, qPCR, and/or RNAscope. MLT levels were quantified with liquid chromatography mass spectrometry. Examination of EPO, EPOR, and MLTR1 at 24 h showed that while placental levels of EPO and MLTR1 mRNA were decreased acutely after CHORIO, cerebral levels of EPO, EPOR and MLTR1 mRNA were increased compared to control. Notably, CHORIO brains at P2 were SIRT1 mRNA deficient with increased HIF1α and HIF2α despite normalized levels of EPO, EPOR and MLTR1, and in the presence of elevated serum EPO levels. Uniquely, brain levels of EPO, EPOR and MLTR1 shifted at P7 and P21, with prominent CHORIO-induced changes in mRNA expression. Reductions at P21 were concomitant with increased serum EPO levels in CHORIO rats compared to controls and variable MLT levels. These data reveal that commensurate with robust inflammation through the maternal placental-fetal axis, CHORIO impacts EPO, MLT, SIRT1, and HIF signal transduction defined by dynamic changes in EPO, EPOR, MLTR1, SIRT1, HIF1α and HIF2α mRNA, and EPO protein. Notably, ligand-receptor mismatch, tissue compartment differential regulation, and non-receptor-mediated signaling highlight the importance, complexity and nuance of neural and immune cell development and provide essential clues to mechanisms of injury in PBI. As the placenta, immune cells, and neural cells share many common, developmentally regulated signal transduction pathways, further studies are needed to clarify the perinatal dynamics of EPO and MLT signaling and to capitalize on therapies that target endogenous neurorepair mechanisms.
PubMed: 37546540
DOI: 10.3389/fphys.2023.1201699