RESUMEN
Placenta-derived stem cells (PDSCs), due to unique traits such as mesenchymal and embryonic characteristics and the absence of ethical constraints, are in a clinically and therapeutically advantageous position. To aid in stemness maintenance, counter pathophysiological stresses, and withstand post-differentiation challenges, stem cells require elevated protein synthesis and consequently augmented proteostasis. Stem cells exhibit source-specific proteostasis traits, making it imperative to study them individually from different sources. These studies have implications for understanding stem cell biology and exploitation in the augmentation of therapeutic applications. Here, we aim to identify the primary determinants of proteotoxic stress response in PDSCs. We generated heat-induced dose-responsive proteotoxic stress models of three stem cell types: placental origin cells, the placenta-derived mesenchymal stem cells (pMSCs), maternal origin cells, the decidua parietalis mesenchymal stem cells (DPMSCs), and the maternal-fetal interface cells, decidua basalis mesenchymal stem cells (DBMSCs), and measured stress induction through biochemical and cell proliferation assays. RT-PCR array analysis of 84 genes involved in protein folding and protein quality control led to the identification of Hsp70 members HSPA1A and HSPA1B as the prominent ones among 17 significantly expressed genes and with further analysis at the protein level through Western blotting. A kinetic analysis of HSPA1A and HSPA1B gene and protein expression allowed a time series evaluation of stress response. As identified by protein expression, an active stress response is in play even at 24 h. More prominent differences in expression between the two homologs are detected at the translational level, alluding to a potential higher requirement for HSPA1B during proteotoxic stress response in PDSCs.
RESUMEN
Mesenchymal stem/stromal cells isolated from human term placenta (pMSCs) have potential to treat clinically manifested inflammatory diseases. Atherosclerosis is a chronic inflammatory disease, and platelets play a contributory role towards its pathogenesis. During transplantation, MSCs interact with platelets and exert influence on their functional outcome. In this study, we investigated the consequences of interaction between pMSCs and platelets, and its impact on platelet-mediated atherosclerosis in vitro. Human platelets were treated with various types of pMSCs either directly or with their secretome, and their effect on agonist-mediated platelet activation and functional characteristics were evaluated. Human umbilical vein endothelial cells (HUVECs) were used as control. The impact of pMSCs treatment on platelets was evaluated by the expression of activation markers and by platelet functional analysis. A subset of pMSCs reduced agonist-induced activation of platelets, both via direct contact and with secretome treatments. Decrease in platelet activation translated into diminished spreading, limited adhesion and minimized aggregation. In addition, pMSCs decreased oxidized LDL (ox-LDL)-inducedCD36-mediated platelet activation, establishing their protective role in atherosclerosis. Gene expression and protein analysis show that pMSCs express pro- and anti-thrombotic proteins, which might be responsible for the modulation of agonist-induced platelet functions. These data suggest the therapeutic benefits of pMSCs in atherosclerosis.
Asunto(s)
Aterosclerosis/metabolismo , Plaquetas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Placenta/citología , Trombosis/metabolismo , Aterosclerosis/etiología , Aterosclerosis/patología , Biomarcadores , Plaquetas/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Técnicas de Cocultivo , Medios de Cultivo Condicionados/metabolismo , Medios de Cultivo Condicionados/farmacología , Susceptibilidad a Enfermedades , Femenino , Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Lipoproteínas LDL/metabolismo , Activación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Embarazo , Trombosis/etiología , Trombosis/patologíaRESUMEN
Disease transmission is dependent on a variety of factors, including the characteristics of an event, such as crowding and shared accommodations, the potential of participants having prolonged exposure and close contact with infectious individuals, the type of activities, and the characteristics of the participants, such as their age and immunity to infectious agents [1-3]. Effective control of outbreaks of infectious diseases requires rapid diagnosis and intervention in high-risk settings. As a result, syndromic and event-based surveillance may be used to enhance the responsiveness of the surveillance system [1]. In public health, surveillance is collecting, analyzing, and interpreting data across time to inform decision-making and aid policy implementation [1]. In this review article we aimed to provide an overview of the principles, types, uses, advantages, and limitations of surveillance systems and to highlight the importance of early warning systems in response to the information received by disease surveillance. The study conducted a comprehensive literature search using several databases, selecting, and reviewing 78 articles that covered different types of surveillance systems, their applications, and their impact on controlling infectious diseases. The article also presents a case study from the Hajj gathering, which highlighted the development, evaluation, and impact of early warning systems on response to the information received by disease surveillance. The study concludes that ongoing disease surveillance should be accompanied by well-designed early warning and response systems, and continuous efforts should be invested in evaluating and validating these systems to minimize the risk of reporting delays and reducing the risk of outbreaks.
Asunto(s)
Enfermedades Transmisibles , Vigilancia de la Población , Humanos , Salud Global , Enfermedades Transmisibles/epidemiología , Brotes de Enfermedades/prevención & control , Salud PúblicaRESUMEN
BACKGROUND: Preeclampsia is a common obstetric syndrome affecting women in their first pregnancy and characterized by hypertension and proteinuria, which appears after 20 weeks of gestation. It is characterized by high blood pressure and occasional damage to another organ system most often the liver and kidneys. Currently, the etiology and pathogenesis of this syndrome are not fully understood. Since mesenchymal stem cells/stromal cells (MSCs) are intimately associated with endothelial cells that line vessel walls in the decidua they may play some role in the pathogenesis of this syndrome. In this study, we have partly, unveiled the mechanism of preeclampsia pathogenesis at the stem cells level. METHODS: We have isolated and characterized MSCs from decidua basalis of preeclampsia placenta (PE-DBMSCs) and showed their decreased functionality in terms of proliferation, migration, adhesion and clone formation potential as compared to MSCs isolated from decidua region of normal placentae (DBMSCs). The cells were preconditioned with H2O2 and the functional characteristics were evaluated. Differentially expressed genes were analyzed using mass spectrometry. Immunoblotting confirmed the expression of these proteins. RESULTS: Pre-conditioning with H2O2 restored the functional outcome of PE-DBMSCs. Mass spectrometry (MS) analysis of differentially expressed proteins revealed HMOX1 as one of the major candidates missing in PE-DBMSCs. HMOX1 inhibition by tin protoporphyrin (SnPP) in normal DBMSCs resulted in a reduction in proliferation, migration, adhesion, and clone formation processes as compared to the untreated controls. mRNA and protein analyses of PE-DBMSCs preconditioned with H2O2 at lower doses showed upregulation of HMOX1 expression. CONCLUSIONS: We hereby show for the first time that loss of function of stem cells/stromal cells isolated from the patients with preeclampsia may contribute towards the disease exacerbation. Our results suggest that HMOX1 may be partially responsible for the loss of functionality in PE-DBMSCs and contribute significantly towards the pathophysiology of preeclampsia. However, further investigation is required to decipher its exact role in the development and onset of the disorder.