Human placenta-derived stromal cells decrease inflammation, placental injury, and blood pressure in hypertensive pregnant mice

Preeclampsia, the development of hypertension and proteinuria or end-organ damage during pregnancy, is a leading cause of both maternal and fetal morbidity and mortality and there are no effective clinical treatments for preeclampsia aside from delivery. The development of preeclampsia is characterized by maladaptation of the maternal immune system, excessive inflammation, and endothelial dysfunction. We have reported that detection of extracellular RNA by Toll-like receptors (TLRs) 3 and 7 is a key initiating signal that contributes to the development of preeclampsia. PLacental eXpanded (PLX-PAD; Pluristem Therapeutics, Inc., Haifa, Israel) cells are human placenta-derived, mesenchymal-like adherent stromal cells that have anti-inflammatory, pro-angiogenic, cytoprotective, and regenerative properties secondary to paracrine secretion of various molecules in response to environmental stimulation. We hypothesized that PLX-PAD cells would reduce the associated inflammation and tissue damage and lower blood pressure in mice with preeclampsia induced by TLR3 or TLR7 activation. Injection of PLX-PAD cells on gestational day 14 significantly decreased systolic blood pressure by day 17 in TLR3-induced and TLR7-induced hypertensive mice (TLR3: 144 to 111 mmHg and TLR7: 145 to 106 mmHg; both p
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research

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ConclusionPolymorphic variants located on the promoter region of AVP are associated with PE. Thus we hypothesize that allelic variation may have a role in increasing the risk of developing PE.
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
Preeclampsia is a common obstetric complication associated with pregnancy and it endangers lives of the mother and the infant. The histopathological changes associated with preeclampsia include systemic endothelial dysfunction, persistent inflammatory state, and coagulation and fibrinolysis dysregulations. Preeclampsia is considered to be caused by the systemic vasoconstriction of small arteries and disruption of the endothelial integrity, resulting in hypertension, proteinuria, and multiple organ dysfunction. However, mediators that trigger or propagate the pathology of preeclampsia remain poorly defined. Syncytiotrophobl...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Abstract There is a large increase in uterine arterial blood flow during normal pregnancy. Structural and cellular adjustments occur in the uterine vasculature during pregnancy to accommodate this increased blood flow through a complex adaptive process that is dependent on multiple coordinated and interactive influences and this process is known as 'vascular remodeling'. The etiology of preeclampsia involves aberrant placentation and vascular remodeling leading to reduced uteroplacental perfusion. The placental ischemia leads to development of hypertension and proteinuria in the mother, intrauterine growth restric...
Source: American Journal of Hypertension - Category: Cardiology Authors: Tags: Am J Hypertens Source Type: research
Abstract BACKGROUND: The hypertensive disorders of pregnancy include pre-eclampsia, gestational hypertension, chronic hypertension, and undefined hypertension. Pre-eclampsia is considerably more prevalent in low-income than in high-income countries. One possible explanation for this discrepancy is dietary differences, particularly calcium deficiency. Calcium supplementation in the second half of pregnancy reduces the serious consequences of pre-eclampsia, but has limited effect on the overall risk of pre-eclampsia. It is important to establish whether calcium supplementation before, and in early pregnancy (before ...
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
Abstract BACKGROUND: The traditional definition of preeclampsia (PE) is based on the development of hypertension and proteinuria. This has recently been revised to include cases without proteinuria but with evidence of renal, hepatic or hematological dysfunction. OBJECTIVE: To examine the impact of the new definition of PE on first, the incidence and severity of the disease, and second, the performance of the competing risks model for first-trimester assessment of risk for PE. METHODS: This was a retrospective study of 66,964 singleton pregnancies that were classified as PE, gestational hypertension (GH)...
Source: The Ultrasound Review of Obstetrics and Gynecology - Category: Radiology Authors: Tags: Ultrasound Obstet Gynecol Source Type: research
CONCLUSIONS The length of hospital stay of women is higher among those belonging to the age group ranging from 15 to 17 years old and for those aged 45 years old or more. The presence of associated comorbidities, such as eclampsia, pre-existing hypertensive disorder with superimposed proteinuria and gestational hypertension (induced by pregnancy) with significant proteinuria increase the length of hospital stay. This study enabled the construction of distinct criticality level profiles based on the combination of age groups and the main comorbidities, which were directly related to the length of hospital stay.RESUMO OBJETI...
Source: Revista de Saude Publica - Category: International Medicine & Public Health Source Type: research
Conclusion: Our results showed that MIR503HG inhibited the proliferation, invasion, and migration of HTR-8/SVneo and JEG3 cells, which may be related to the pathogenesis of PE. PMID: 31467616 [PubMed - in process]
Source: Disease Markers - Category: Laboratory Medicine Tags: Dis Markers Source Type: research
Abstract Preeclampsia is a pregnancy-induced condition that impairs mother's health and results in pregnancy termination or premature delivery. Elevated levels of placenta-derived extracellular vesicles in the circulation have been consistently associated with preeclampsia, but whether placenta-derived extracellular vesicles induce preeclampsia or are merely the product of preeclampsia is not known. Guided by a small cohort study of preeclampsia patients, we examined the impact of placenta-derived extracellular vesicles on the pathogenesis of preeclampsia in mouse models. We found that placenta-derived extracellul...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Authors: Li X, Fang Y Abstract Preeclampsia is a complication of pregnancy characterized by new-onset hypertension and proteinuria of gestation, with serious consequences for mother and infant. Although a vast amount of research has been performed on the pathogenesis of preeclampsia, the underlying mechanisms of this multisystemic disease have remained to be fully elucidated. Data were retrieved from Gene Expression Omnibus database GSE40182 dataset. After data preprocessing, differentially expressed genes of placental cells cultured in vitro from preeclampsia and normal pregnancy were determined and subjected to K...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
In this study, we performed a multi-step bioinformatics analysis of microarray data for identifying hub genes as diagnostic biomarkers of preeclampsia. With the help of gene expression profiles of the Gene Expression Omnibus (GEO) dataset GSE60438, a total of 268 dysregulated genes were identified including 131 up- and 137 downregulated differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs suggested that DEGs were significantly enriched in disease-related biological processes such as hormone activity, immune response, steroid hormone...
Source: Bioscience Reports - Category: Biomedical Science Authors: Tags: Biosci Rep Source Type: research
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