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Vincent Yeung - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stromal cell derived extracellular vesicle therapy prevents preeclamptic physiology through intrauterine immunomodulation
Biology of Reproduction, 2021Co-Authors: Elizabeth S Taglauer, Angeles Fernandezgonzalez, Gareth R Willis, Monica Reis, Vincent YeungAbstract:Human umbilical cord-derived mesenchymal stromal cells (MSCs) are a widely recognized treatment modality for a variety of preclinical disease models and have been transitioned to human clinical trials. We have previously shown in neonatal lung disease that the therapeutic capacity of MSCs is conferred by their secreted extracellular vesicles (MEx), which function primarily through immunomodulation. We hypothesize that MEx have significant therapeutic potential pertinent to immune-mediated gestational diseases. Of particular interest is early-onset preeclampsia, which can be caused by alterations of the maternal intrauterine immune environment. Using a heme-oxygenase-1 null mouse model of pregnancy loss with preeclampsia-like features, we examined the preventative effects of maternal MEx treatment early in pregnancy. Heme oxygenase-1 null females (HMOX1-/-) or wild-type control females were bred in homozygous matings followed by evaluation of maternal and fetal parameters. A single dose of MEx was administered intravenously on gestational day (GD)1 to HMOX1-/- females (HMOX1-/- MEx). Compared with untreated HMOX1-/- females, HMOX1-/- MEx-treated pregnancies showed significant improvement in fetal loss, intrauterine growth restriction, placental spiral artery modification, and maternal preeclamptic stigmata. Biodistribution studies demonstrated that MEx localize to a subset of cells in the preimplantation uterus. Further, mass cytometric (CyTOF) evaluation of utero-placental leukocytes in HMOX1-/- MEx versus untreated pregnancies showed alteration in the abundance, surface marker repertoire, and cytokine profiles of multiple immune populations. Our data demonstrate the therapeutic potential of MEx to optimize the intrauterine immune environment and prevent maternal and fetal sequelae of preeclamptic disease.
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mesenchymal stromal cell derived extracellular vesicle therapy prevents preeclamptic physiology through intrauterine immunomodulation
Biology of Reproduction, 2020Co-Authors: Elizabeth S Taglauer, Angeles Fernandezgonzalez, Gareth R Willis, Monica Reis, Vincent YeungAbstract:Human umbilical cord-derived mesenchymal stromal cells (MSCs) are a widely recognized treatment modality for a variety of pre-clinical disease models and have been transitioned to human clinical trials. We have previously shown in neonatal lung disease that the therapeutic capacity of MSCs is conferred by their secreted extracellular vesicles (MEx), which function primarily through immunomodulation. We hypothesize MEx have significant therapeutic potential pertinent to immune-mediated gestational diseases. Of particular interest is early-onset preeclampsia, which can be caused by alterations of the maternal intrauterine immune environment. Using a heme-oxygenase-1 null mouse model of pregnancy loss with preeclamptic features, we examined the preventative effects of maternal MEx treatment early in pregnancy. Heme oxygenase-1 null females (HMOX1-/-) or wild type (WT) control females were bred in homozygous matings followed by evaluation of maternal and fetal parameters. A single dose of MEx was administered intravenously on gestational day 1 to HMOX1-/- females (HMOX1-/- MEx). Compared to untreated HMOX1-/- females, HMOX1-/- MEx treated pregnancies showed significant improvement in fetal loss, intrauterine growth restriction, placental spiral artery modification and maternal preeclamptic stigmata. Biodistribution studies demonstrated that MEx localize to a subset of cells in the preimplantation uterus. Further, mass cytometric (CyTOF) evaluation of utero-placental leukocytes in HMOX1-/- MEx vs untreated pregnancies showed alteration in the abundance, surface marker repertoire and cytokine profiles of multiple immune populations. Our data demonstrate the therapeutic potential of MEx to optimize the intrauterine immune environment and prevent maternal and fetal sequelae of preeclamptic disease.
Libor Vítek - One of the best experts on this subject based on the ideXlab platform.
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Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition
Hindawi Limited, 2018Co-Authors: Václav Šmíd, Jakub Šuk, Neli Kachamakova-trojanowska, Jana Jašprová, Petra Valášková, Alicja Józkowicz, Józef Dulak, František Šmíd, Libor Vítek, Lucie MuchováAbstract:Heme oxygenase 1 (HMOX1), a ubiquitous enzyme degrading heme to carbon monoxide, iron, and biliverdin, is one of the cytoprotective enzymes induced in response to a variety of stimuli, including cellular oxidative stress. Gangliosides, sialic acid-containing glycosphingolipids expressed in all cells, are involved in cell recognition, signalling, and membrane stabilization. Their expression is often altered under many pathological and physiological conditions including cell death, proliferation, and differentiation. The aim of this study was to assess the possible role of HMOX1 in ganglioside metabolism in relation to oxidative stress. The content of liver and brain gangliosides, their cellular distribution, and mRNA as well as protein expression of key glycosyltransferases were determined in HMOX1 knockout mice as well as their wild-type littermates. To elucidate the possible underlying mechanisms between HMOX1 and ganglioside metabolism, hepatoblastoma HepG2 and neuroblastoma SH-SY5Y cell lines were used for in vitro experiments. Mice lacking HMOX1 exhibited a significant increase in concentrations of liver and brain gangliosides and in mRNA expression of the key enzymes of ganglioside metabolism. A marked shift of GM1 ganglioside from the subsinusoidal part of the intracellular compartment into sinusoidal membranes of hepatocytes was shown in HMOX1 knockout mice. Induction of oxidative stress by chenodeoxycholic acid in vitro resulted in a significant increase in GM3, GM2, and GD1a gangliosides in SH-SY5Y cells and GM3 and GM2 in the HepG2 cell line. These changes were abolished with administration of bilirubin, a potent antioxidant agent. These observations were closely related to oxidative stress-mediated changes in sialyltransferase expression regulated at least partially through the protein kinase C pathway. We conclude that oxidative stress is an important factor modulating synthesis and distribution of gangliosides in vivo and in vitro which might affect ganglioside signalling in higher organisms
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serum bilirubin levels and promoter variations in HMOX1 and ugt1a1 genes in patients with fabry disease
Oxidative Medicine and Cellular Longevity, 2017Co-Authors: Alena Jiraskova, Giulia Bortolussi, Gabriela Dostalova, Lenka Eremiasova, Lubor Golaň, Vilem Danzig, Ales Linhart, Libor VítekAbstract:The aim of our study was to assess the possible relationships among heme oxygenase (HMOX), bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variations, serum bilirubin levels, and Fabry disease (FD). The study included 56 patients with FD (M : F ratio = 0.65) and 185 healthy individuals. Complete standard laboratory and clinical work-up was performed on all subjects, together with the determination of total peroxyl radical-scavenging capacity. The (GT)n and (TA)n dinucleotide variations in the HMOX1 and UGT1A1 gene promoters, respectively, were determined by DNA fragment analysis. Compared to controls, patients with FD had substantially lower serum bilirubin levels (12.0 versus 8.85 μmol/L, ) and also total antioxidant capacity ( ), which showed a close positive relationship with serum bilirubin levels ( ) and the use of enzyme replacement therapy ( ). There was no association between HMOX1 gene promoter polymorphism and manifestation of FD. However, the presence of the TA7 allele UGT1A1 gene promoter, responsible for higher systemic bilirubin levels, was associated with a twofold lower risk of manifestation of FD (OR = 0.51, 95% CI = 0.27–0.97, ). Markedly lower serum bilirubin levels in FD patients seem to be due to bilirubin consumption during increased oxidative stress, although UGT1A1 promoter gene polymorphism may modify the manifestation of FD as well.
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Expression of Biliverdin Reductase A in Peripheral Blood Leukocytes Is Associated with Treatment Response in HCV-Infected Patients
2016Co-Authors: Iva Subhanova, Libor Vítek, Lucie Muchová, Martin Lenicek, Hendrik J Vreman, Ondrej Luksan, Kristyna Kubickova, Miluse Kreidlova, Tomas Zima, Petr UrbanekAbstract:Background and Aims: Hepatitis C virus (HCV) infection is associated with systemic oxidative stress. Since the heme catabolic pathway plays an important role in antioxidant protection, we attempted to assess the gene expression of key enzymes of heme catabolism, heme oxygenase 1 (HMOX1), heme oxygenase 2 (HMOX2), and biliverdin reductase A (BLVRA) in the liver and peripheral blood leukocytes (PBL) of patients chronically infected with HCV. Methods: Gene expressions (HMOX1, HMOX2, BLVRA) and HCV RNA were analyzed in PBL of HCV treatment naı̈ve patients (n = 58) and controls (n = 55), with a subset of HCV patients having data on hepatic gene expression (n = 35). Based upon the therapeutic outcome, HCV patients were classified as either responders (n = 38) or treatment-failure patients (n = 20). Blood samples in HCV patients were collected at day 0, and week 12, 24, 36, and 48 after the initiation of standard antiviral therapy. Results: Compared to the controls, substantially increased BLVRA expression was detected in PBL (p,0.001) of therapeutically naı̈ve HCV patients. mRNA levels of BLVRA in PBL closely correlated with those in liver tissue (r2 = 0.347,p = 0.03). A marked difference in BLVRA expression in PBL between the sustained responders and patients with treatment failure was detected at week 0 and during the follow-up (p,0.001). Multivariate analysis revealed that BLVRA basal expression in PBL was an independent predictor for sustained virological response (OR 15; 95 % CI 1.05–214.2
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spirulina platensis and phycocyanobilin activate atheroprotective heme oxygenase 1 a possible implication for atherogenesis
Food & Function, 2013Co-Authors: Zbynek Strasky, Lucie Muchová, Lenka Zemankova, Ivana Nemeckova, Jana Rathouska, Ronald J Wong, Iva Subhanova, Jana Vanikova, Katerina Vanova, Libor VítekAbstract:Spirulina platensis, a water blue-green alga, has been associated with potent biological effects, which might have important relevance in atheroprotection. We investigated whether S. platensis or phycocyanobilin (PCB), its tetrapyrrolic chromophore, can activate atheroprotective heme oxygenase-1 (HMOX1), a key enzyme in the heme catabolic pathway responsible for generation of a potent antioxidant bilirubin, in endothelial cells and in a mouse model of atherosclerosis. In vitro experiments were performed on EA.hy926 endothelial cells exposed to extracts of S. platensis or PCB. In vivo studies were performed on ApoE-deficient mice fed a cholesterol diet and S. platensis. The effect of these treatments on HMOX1, as well as other markers of oxidative stress and endothelial dysfunction, was then investigated. Both S. platensis and PCB markedly upregulated HMOX1 in vitro, and a substantial overexpression of HMOX1 was found in aortic atherosclerotic lesions of ApoE-deficient mice fed S. platensis. In addition, S. platensis treatment led to a significant increase in HMOX1 promoter activity in the spleens of Hmox-luc transgenic mice. Furthermore, both S. platensis and PCB were able to modulate important markers of oxidative stress and endothelial dysfunction, such as eNOS, p22 NADPH oxidase subunit, and/or VCAM-1. Both S. platensis and PCB activate atheroprotective HMOX1 in endothelial cells and S. platensis increased the expression of HMOX1 in aortic atherosclerotic lesions in ApoE-deficient mice, and also in Hmox-luc transgenic mice beyond the lipid lowering effect. Therefore, activation of HMOX1 and the heme catabolic pathway may represent an important mechanism of this food supplement for the reduction of atherosclerotic disease.
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expression of biliverdin reductase a in peripheral blood leukocytes is associated with treatment response in hcv infected patients
PLOS ONE, 2013Co-Authors: Iva Subhanova, Libor Vítek, Lucie Muchová, Martin Lenicek, Hendrik J Vreman, Ondrej Luksan, Kristyna Kubickova, Miluse Kreidlova, Tomas Zima, Petr UrbanekAbstract:Background and Aims Hepatitis C virus (HCV) infection is associated with systemic oxidative stress. Since the heme catabolic pathway plays an important role in antioxidant protection, we attempted to assess the gene expression of key enzymes of heme catabolism, heme oxygenase 1 (HMOX1), heme oxygenase 2 (HMOX2), and biliverdin reductase A (BLVRA) in the liver and peripheral blood leukocytes (PBL) of patients chronically infected with HCV. Methods Gene expressions (HMOX1, HMOX2, BLVRA) and HCV RNA were analyzed in PBL of HCV treatment naive patients (n = 58) and controls (n = 55), with a subset of HCV patients having data on hepatic gene expression (n = 35). Based upon the therapeutic outcome, HCV patients were classified as either responders (n = 38) or treatment-failure patients (n = 20). Blood samples in HCV patients were collected at day 0, and week 12, 24, 36, and 48 after the initiation of standard antiviral therapy. Results Compared to the controls, substantially increased BLVRA expression was detected in PBL (p<0.001) of therapeutically naive HCV patients. mRNA levels of BLVRA in PBL closely correlated with those in liver tissue (r2 = 0.347,p = 0.03). A marked difference in BLVRA expression in PBL between the sustained responders and patients with treatment failure was detected at week 0 and during the follow-up (p<0.001). Multivariate analysis revealed that BLVRA basal expression in PBL was an independent predictor for sustained virological response (OR 15; 95% CI 1.05–214.2; P = 0.046). HMOX1/2 expression did not have any effect on the treatment outcome. Conclusion Our results suggest that patients with chronic HCV infection significantly upregulate BLVRA expression in PBL. The lack of BLVRA overexpression is associated with non-responsiveness to standard antiviral therapy; whereas, HMOX1/2 does not seem to have any predictive potential.
Elizabeth S Taglauer - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stromal cell derived extracellular vesicle therapy prevents preeclamptic physiology through intrauterine immunomodulation
Biology of Reproduction, 2021Co-Authors: Elizabeth S Taglauer, Angeles Fernandezgonzalez, Gareth R Willis, Monica Reis, Vincent YeungAbstract:Human umbilical cord-derived mesenchymal stromal cells (MSCs) are a widely recognized treatment modality for a variety of preclinical disease models and have been transitioned to human clinical trials. We have previously shown in neonatal lung disease that the therapeutic capacity of MSCs is conferred by their secreted extracellular vesicles (MEx), which function primarily through immunomodulation. We hypothesize that MEx have significant therapeutic potential pertinent to immune-mediated gestational diseases. Of particular interest is early-onset preeclampsia, which can be caused by alterations of the maternal intrauterine immune environment. Using a heme-oxygenase-1 null mouse model of pregnancy loss with preeclampsia-like features, we examined the preventative effects of maternal MEx treatment early in pregnancy. Heme oxygenase-1 null females (HMOX1-/-) or wild-type control females were bred in homozygous matings followed by evaluation of maternal and fetal parameters. A single dose of MEx was administered intravenously on gestational day (GD)1 to HMOX1-/- females (HMOX1-/- MEx). Compared with untreated HMOX1-/- females, HMOX1-/- MEx-treated pregnancies showed significant improvement in fetal loss, intrauterine growth restriction, placental spiral artery modification, and maternal preeclamptic stigmata. Biodistribution studies demonstrated that MEx localize to a subset of cells in the preimplantation uterus. Further, mass cytometric (CyTOF) evaluation of utero-placental leukocytes in HMOX1-/- MEx versus untreated pregnancies showed alteration in the abundance, surface marker repertoire, and cytokine profiles of multiple immune populations. Our data demonstrate the therapeutic potential of MEx to optimize the intrauterine immune environment and prevent maternal and fetal sequelae of preeclamptic disease.
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mesenchymal stromal cell derived extracellular vesicle therapy prevents preeclamptic physiology through intrauterine immunomodulation
Biology of Reproduction, 2020Co-Authors: Elizabeth S Taglauer, Angeles Fernandezgonzalez, Gareth R Willis, Monica Reis, Vincent YeungAbstract:Human umbilical cord-derived mesenchymal stromal cells (MSCs) are a widely recognized treatment modality for a variety of pre-clinical disease models and have been transitioned to human clinical trials. We have previously shown in neonatal lung disease that the therapeutic capacity of MSCs is conferred by their secreted extracellular vesicles (MEx), which function primarily through immunomodulation. We hypothesize MEx have significant therapeutic potential pertinent to immune-mediated gestational diseases. Of particular interest is early-onset preeclampsia, which can be caused by alterations of the maternal intrauterine immune environment. Using a heme-oxygenase-1 null mouse model of pregnancy loss with preeclamptic features, we examined the preventative effects of maternal MEx treatment early in pregnancy. Heme oxygenase-1 null females (HMOX1-/-) or wild type (WT) control females were bred in homozygous matings followed by evaluation of maternal and fetal parameters. A single dose of MEx was administered intravenously on gestational day 1 to HMOX1-/- females (HMOX1-/- MEx). Compared to untreated HMOX1-/- females, HMOX1-/- MEx treated pregnancies showed significant improvement in fetal loss, intrauterine growth restriction, placental spiral artery modification and maternal preeclamptic stigmata. Biodistribution studies demonstrated that MEx localize to a subset of cells in the preimplantation uterus. Further, mass cytometric (CyTOF) evaluation of utero-placental leukocytes in HMOX1-/- MEx vs untreated pregnancies showed alteration in the abundance, surface marker repertoire and cytokine profiles of multiple immune populations. Our data demonstrate the therapeutic potential of MEx to optimize the intrauterine immune environment and prevent maternal and fetal sequelae of preeclamptic disease.
Angeles Fernandezgonzalez - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stromal cell derived extracellular vesicle therapy prevents preeclamptic physiology through intrauterine immunomodulation
Biology of Reproduction, 2021Co-Authors: Elizabeth S Taglauer, Angeles Fernandezgonzalez, Gareth R Willis, Monica Reis, Vincent YeungAbstract:Human umbilical cord-derived mesenchymal stromal cells (MSCs) are a widely recognized treatment modality for a variety of preclinical disease models and have been transitioned to human clinical trials. We have previously shown in neonatal lung disease that the therapeutic capacity of MSCs is conferred by their secreted extracellular vesicles (MEx), which function primarily through immunomodulation. We hypothesize that MEx have significant therapeutic potential pertinent to immune-mediated gestational diseases. Of particular interest is early-onset preeclampsia, which can be caused by alterations of the maternal intrauterine immune environment. Using a heme-oxygenase-1 null mouse model of pregnancy loss with preeclampsia-like features, we examined the preventative effects of maternal MEx treatment early in pregnancy. Heme oxygenase-1 null females (HMOX1-/-) or wild-type control females were bred in homozygous matings followed by evaluation of maternal and fetal parameters. A single dose of MEx was administered intravenously on gestational day (GD)1 to HMOX1-/- females (HMOX1-/- MEx). Compared with untreated HMOX1-/- females, HMOX1-/- MEx-treated pregnancies showed significant improvement in fetal loss, intrauterine growth restriction, placental spiral artery modification, and maternal preeclamptic stigmata. Biodistribution studies demonstrated that MEx localize to a subset of cells in the preimplantation uterus. Further, mass cytometric (CyTOF) evaluation of utero-placental leukocytes in HMOX1-/- MEx versus untreated pregnancies showed alteration in the abundance, surface marker repertoire, and cytokine profiles of multiple immune populations. Our data demonstrate the therapeutic potential of MEx to optimize the intrauterine immune environment and prevent maternal and fetal sequelae of preeclamptic disease.
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mesenchymal stromal cell derived extracellular vesicle therapy prevents preeclamptic physiology through intrauterine immunomodulation
Biology of Reproduction, 2020Co-Authors: Elizabeth S Taglauer, Angeles Fernandezgonzalez, Gareth R Willis, Monica Reis, Vincent YeungAbstract:Human umbilical cord-derived mesenchymal stromal cells (MSCs) are a widely recognized treatment modality for a variety of pre-clinical disease models and have been transitioned to human clinical trials. We have previously shown in neonatal lung disease that the therapeutic capacity of MSCs is conferred by their secreted extracellular vesicles (MEx), which function primarily through immunomodulation. We hypothesize MEx have significant therapeutic potential pertinent to immune-mediated gestational diseases. Of particular interest is early-onset preeclampsia, which can be caused by alterations of the maternal intrauterine immune environment. Using a heme-oxygenase-1 null mouse model of pregnancy loss with preeclamptic features, we examined the preventative effects of maternal MEx treatment early in pregnancy. Heme oxygenase-1 null females (HMOX1-/-) or wild type (WT) control females were bred in homozygous matings followed by evaluation of maternal and fetal parameters. A single dose of MEx was administered intravenously on gestational day 1 to HMOX1-/- females (HMOX1-/- MEx). Compared to untreated HMOX1-/- females, HMOX1-/- MEx treated pregnancies showed significant improvement in fetal loss, intrauterine growth restriction, placental spiral artery modification and maternal preeclamptic stigmata. Biodistribution studies demonstrated that MEx localize to a subset of cells in the preimplantation uterus. Further, mass cytometric (CyTOF) evaluation of utero-placental leukocytes in HMOX1-/- MEx vs untreated pregnancies showed alteration in the abundance, surface marker repertoire and cytokine profiles of multiple immune populations. Our data demonstrate the therapeutic potential of MEx to optimize the intrauterine immune environment and prevent maternal and fetal sequelae of preeclamptic disease.
Gareth R Willis - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stromal cell derived extracellular vesicle therapy prevents preeclamptic physiology through intrauterine immunomodulation
Biology of Reproduction, 2021Co-Authors: Elizabeth S Taglauer, Angeles Fernandezgonzalez, Gareth R Willis, Monica Reis, Vincent YeungAbstract:Human umbilical cord-derived mesenchymal stromal cells (MSCs) are a widely recognized treatment modality for a variety of preclinical disease models and have been transitioned to human clinical trials. We have previously shown in neonatal lung disease that the therapeutic capacity of MSCs is conferred by their secreted extracellular vesicles (MEx), which function primarily through immunomodulation. We hypothesize that MEx have significant therapeutic potential pertinent to immune-mediated gestational diseases. Of particular interest is early-onset preeclampsia, which can be caused by alterations of the maternal intrauterine immune environment. Using a heme-oxygenase-1 null mouse model of pregnancy loss with preeclampsia-like features, we examined the preventative effects of maternal MEx treatment early in pregnancy. Heme oxygenase-1 null females (HMOX1-/-) or wild-type control females were bred in homozygous matings followed by evaluation of maternal and fetal parameters. A single dose of MEx was administered intravenously on gestational day (GD)1 to HMOX1-/- females (HMOX1-/- MEx). Compared with untreated HMOX1-/- females, HMOX1-/- MEx-treated pregnancies showed significant improvement in fetal loss, intrauterine growth restriction, placental spiral artery modification, and maternal preeclamptic stigmata. Biodistribution studies demonstrated that MEx localize to a subset of cells in the preimplantation uterus. Further, mass cytometric (CyTOF) evaluation of utero-placental leukocytes in HMOX1-/- MEx versus untreated pregnancies showed alteration in the abundance, surface marker repertoire, and cytokine profiles of multiple immune populations. Our data demonstrate the therapeutic potential of MEx to optimize the intrauterine immune environment and prevent maternal and fetal sequelae of preeclamptic disease.
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mesenchymal stromal cell derived extracellular vesicle therapy prevents preeclamptic physiology through intrauterine immunomodulation
Biology of Reproduction, 2020Co-Authors: Elizabeth S Taglauer, Angeles Fernandezgonzalez, Gareth R Willis, Monica Reis, Vincent YeungAbstract:Human umbilical cord-derived mesenchymal stromal cells (MSCs) are a widely recognized treatment modality for a variety of pre-clinical disease models and have been transitioned to human clinical trials. We have previously shown in neonatal lung disease that the therapeutic capacity of MSCs is conferred by their secreted extracellular vesicles (MEx), which function primarily through immunomodulation. We hypothesize MEx have significant therapeutic potential pertinent to immune-mediated gestational diseases. Of particular interest is early-onset preeclampsia, which can be caused by alterations of the maternal intrauterine immune environment. Using a heme-oxygenase-1 null mouse model of pregnancy loss with preeclamptic features, we examined the preventative effects of maternal MEx treatment early in pregnancy. Heme oxygenase-1 null females (HMOX1-/-) or wild type (WT) control females were bred in homozygous matings followed by evaluation of maternal and fetal parameters. A single dose of MEx was administered intravenously on gestational day 1 to HMOX1-/- females (HMOX1-/- MEx). Compared to untreated HMOX1-/- females, HMOX1-/- MEx treated pregnancies showed significant improvement in fetal loss, intrauterine growth restriction, placental spiral artery modification and maternal preeclamptic stigmata. Biodistribution studies demonstrated that MEx localize to a subset of cells in the preimplantation uterus. Further, mass cytometric (CyTOF) evaluation of utero-placental leukocytes in HMOX1-/- MEx vs untreated pregnancies showed alteration in the abundance, surface marker repertoire and cytokine profiles of multiple immune populations. Our data demonstrate the therapeutic potential of MEx to optimize the intrauterine immune environment and prevent maternal and fetal sequelae of preeclamptic disease.