Targeting senescence improves angiogenic potential of adipose-derived mesenchymal stem cells in patients with preeclampsia

AbstractBackgroundPreeclampsia is a pregnancy-specific hypertensive disorder characterized by impaired angiogenesis. We postulate that senescence of mesenchymal stem cells (MSC), multipotent cells with pro-angiogenic activities, is one of the mechanisms by which systemic inflammation exerts inhibitory effects on angiogenesis in preeclampsia.MethodsMSC were isolated from abdominal fat tissue explants removed during medically indicated C-sections from women with preeclampsia (PE-MSC,n = 10) and those with normotensive pregnancies (NP-MSC,n = 12). Sections of the frozen subcutaneous adipose tissue were assessed for inflammation by staining for tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1. Viability, proliferation, and migration were compared between PE-MSC vs. NP-MSC. Apoptosis and angiogenesis we re assayed before and after treatment with a senolytic agent (1 μM dasatinib) using the IncuCyte S3 Live-Cell Analysis System. Similarly, staining for senescence-associated beta galactosidase (SABG) and qPCR for gene expression of senescence markers, p16 and p21, as well as senescence-associated secretory phenotype (SASP) components, IL-6, IL-8, MCP-1, and PAI-1, were studied before and after treatment with dasatinib and compared between PE and NP.ResultsAfter in vitro exposure to TNF-alpha, MSC demonstrated upregulation of SASP components, including interleukins-6 and -8 and MCP-1. Staining of the subcutaneous adi...
Source: Biology of Sex Differences - Category: Biology Source Type: research

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Publication date: 12 November 2019Source: Stem Cell Reports, Volume 13, Issue 5Author(s): Joseph M. McCune, Irving L. WeissmanSome have argued that human fetal tissue research is unnecessary and/or immoral. Recently, the Trump administration has taken the drastic––and we believe misguided––step to effectively ban government-funded research on fetal tissue altogether. In this article, we show that entire lines of research and their clinical outcomes would not have progressed had fetal tissue been unavailable. We argue that this research has been carried out in a manner that is ethical and legal, and ...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
Purpose of review To investigate the JZE alterations in gynecological and obstetrical disorders and impact on diagnosis, prognosis and treatment. Recent findings JZE was found to be significantly extended in patients with endometriosis, leading to the conclusion that endometriosis is a primary disease of the uterus, much like adenomyosis. Statistical correlation was then demonstrated between the severity of endometriosis and the depth of the adenomyosis infiltrates, hence the thickening of the JZE. Stem cells, predominantly found in the JZE were also found in histological sections of leiomyoma, suggested to be the ori...
Source: Current Opinion in Obstetrics and Gynecology - Category: OBGYN Tags: WOMEN'S HEALTH: Edited by Joseph Aquilina Source Type: research
Abstract The stem cell exchange during pregnancy is thought to remain chimeras for life. Few studies recently revealed that maternal transfer of viable stem cells to the offspring continues even after birth during breastfeeding. Some of these stem cells are likely to integrate into different organs (brain, blood, kidneys, and pancreas), including neurons and insulin-producing cells in the pancreas to become functional cells. This finding opens a new avenue for research on therapeutic uses of breast milk-derived stem cells. Recently Dr. Foteini Hassiotou used glowing mice, which were genetically modified to express...
Source: Current Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Curr Stem Cell Res Ther Source Type: research
ConclusionFindings are consistent with a low rate of RTX interruptions, with pregnancy and adverse events as most frequent reasons. A small proportion of patients switched due to breakthrough disease in context of incomplete B-lymphocyte depletion. Signs of ongoing disease activity in the remaining group was low regardless of whether a new DMT was started. These findings are consistent with a long acting effect of RTX in RRMS and absence of rebound disease activity phenomena upon stopping therapy.
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
ConclusionsThis meta-analysis reflects low pregnancy rates for cancer survivors desiring a family. However, live births are improving over time with new technology and novel therapies. Hence, female cancer patients should be offered timely discussions, counselling and education around fertility preservation options prior to starting treatment with gonadotoxic therapy.
Source: Supportive Care in Cancer - Category: Cancer & Oncology Source Type: research
The expression ofRIG-1 in placenta samples was assessed in women of reproductive age with early- and late-onset preeclampsia and cesarean delivery at 27-39 weeks of gestation. The highest expression ofRIG-1 was found in the syncytiotrophoblast of placental villi in the group with uncomplicated full-term pregnancy (normal);RIG-1 expression in groups with early- and late-onset preeclampsia was significantly (p
Source: Bulletin of Experimental Biology and Medicine - Category: Biology Source Type: research
ConclusionFindings are consistent with a low rate of RTX interruptions, with pregnancy and adverse events as most frequent reasons. A small proportion of patients switched due to breakthrough disease in context of incomplete B-lymphocyte depletion. Signs of ongoing disease activity in the remaining group was low regardless of whether a new DMT was started. These findings are consistent with a long acting effect of RTX in RRMS and absence of rebound disease activity phenomena upon stopping therapy.
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
In this study, AT1-AAs were detected in the sera of patients with peripheral arterial disease (PAD) and the positive rate was 44.44% vs. 17.46% in non-PAD volunteers. In addition, analysis showed that AT1-AAs level was positively correlated with PAD. To reveal the causal relationship between AT1-AAs and vascular aging, an AT1-AAs-positive rat model was established by active immunization. The carotid pulse wave velocity was higher, and the aortic endothelium-dependent vasodilatation was attenuated significantly in the immunized rats. Morphological staining showed thickening of the aortic wall. Histological examination showe...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Contributors : Paul Soumen ; Bhattacharya BhaswatiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAtypical protein kinase C iota (Prkci) knockout mice are embryonic lethal at gestation day 9.5 but the underlying molecular mechanisms is not known. Here , using Prkci knockout mouse model , we show that trophectoderm specific function of PKCi is essential for post-implantation mammalian development. We observed that PKCi is expressed predominantly in the trophectoderm lineage and developing placenta region in post-implantation mouse embryos. Prkci knockout or homozygous embryos show seve...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
This study aimed to survey the effects of rat neonatal CSF collected from induced hypothyroid mothers on differentiation of bone marrow mesenchymal stem cells (BM-MSCs). We hypothesized that hypothyroidism affected levels of growth factor in CSF. To induce hypothyroidism, pregnant Wistar rats received methimazole at the third day of gestation. BM-MSCs were obtained from rat femurs and tibias and cultured in medium. CSF was collected from the cisterna magna of newborn rats, and cells were subsequently exposed to CSF with concentrations of 5,7, and 10 /100 (v/v) for 72 h. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazo...
Source: Acta Neurobiologiae Experimentalis - Category: Neurology Authors: Tags: Acta Neurobiol Exp (Wars) Source Type: research
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