scholarly journals Role of tissue factor in the procoagulant and antibacterial effects of human adipose-derived mesenchymal stem cells during pneumosepsis in mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Desirée Perlee ◽  
Alex F. de Vos ◽  
Brendon P. Scicluna ◽  
Anja Maag ◽  
Pablo Mancheño ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Factor ◽  
Procoagulant Activity ◽  
Experimental Sepsis ◽  
Late Time ◽  
Antibacterial Effects ◽  
Coagulation Activation ◽  
Adult Mesenchymal Stem Cells

Abstract Background Adult mesenchymal stem cells (MSCs) improve the host response during experimental sepsis in animals. MSCs from various sources express a procoagulant activity that has been linked to the expression of tissue factor. This study sought to determine the role of tissue factor associated with adipose-derived MSCs (ASCs) in their procoagulant and antibacterial effects during pneumonia-derived sepsis. Methods Mice were infused intravenously with ASCs or vehicle after infection with the common human pathogen Klebsiella pneumoniae via the airways. Results Infusion of freshly cultured or cryopreserved ASCs induced the expression of many genes associated with tissue factor signaling and coagulation activation in the lungs. Freshly cultured and cryopreserved ASCs, as well as ASC lysates, exerted procoagulant activity in vitro as determined by a fibrin generation assay, which was almost completely inhibited by an anti-tissue factor antibody. Infusion of cryopreserved ASCs was associated with a rise in plasma thrombin-antithrombin complexes (indicative of coagulation activation) and formation of multiple thrombi in the lungs 4 h post-infusion. Preincubation of ASCs with anti-tissue factor antibody prior to infusion prevented the rise in plasma thrombin-antithrombin complex concentrations but did not influence thrombus formation in the lungs. ASCs reduced bacterial loads in the lungs and liver at 48 h after infection, which was not influenced by preincubation with anti-tissue factor antibody. At this late time point, microthrombi in the lungs were not detected anymore. Conclusion These data indicate that ASC-associated tissue factor is responsible for systemic activation of coagulation after infusion of ASCs but not for the formation of microthrombi in the lungs or antibacterial effects.

scholarly journals Correction: The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs)

2019 ◽  
Vol 7 (9) ◽  
pp. 3926-3926 ◽  
Author(s):  
Xianfang Jiang ◽  
Xianyuan Huang ◽  
Tongmeng Jiang ◽  
Li Zheng ◽  
Jinmin Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chondrogenic Differentiation ◽  
Collagen Hydrogel ◽  
Adult Mesenchymal Stem Cells

Correction for ‘The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs)’ by Xianfang Jiang, et al., Biomater. Sci., 2018, 6, 1556–1568.

Biologics in Shoulder Surgery: The Role of Adult Mesenchymal Stem Cells in Tendon Repair

2007 ◽  
Vol 22 (1) ◽  
pp. 2-9 ◽  
Author(s):  
Clifford G. Rios ◽  
Mary Beth McCarthy ◽  
Cristina Arciero ◽  
Jeffrey T. Spang ◽  
Robert A. Arciero ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tendon Repair ◽  
Shoulder Surgery ◽  
Adult Mesenchymal Stem Cells

scholarly journals Role of Tissue Factor in Mycobacterium Tuberculosis-induced Inflammation and Disease Pathogenesis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1505-1505
Author(s):  
Kothari Hema ◽  
Shiva Keshava ◽  
Rit Vatsyayan ◽  
Nigel Mackman ◽  
Usha R Pendurthi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tissue Factor ◽  
Host Defense ◽  
Bacterial Infections ◽  
Procoagulant Activity ◽  
Bacterial Burden ◽  
Coagulation Activation ◽  
Aberrant Expression ◽  
Intravascular Coagulation

Abstract Tuberculosis, a chronic lung infection caused by Mycobacterium tuberculosis (M.tb), affects nearly one third of the world’s population. Clinical manifestations of TB include hypercoagulable states and thrombotic complications particularly disseminated intravascular coagulation and deep vein thrombosis. Tissue factor (TF) plays an important role in the initiation of inflammation-induced coagulation. Various bacterial infections induce aberrant expression of TF on vascular cells, which contributes to intravascular coagulation and exacerbation of inflammation. Studies have shown that either a genetic deficiency of TF or blockade of TF functional activity reduces coagulopathy, proinflammatory cytokine release and infection-associated mortality. In contrast, TF-dependent coagulation activation and fibrin deposition may be protective in host-defense against certain bacterial infections via reducing pathogen burden and limiting their dissemination. In vitro M.tb infection markedly upregulates TF expression and increases procoagulant activity of macrophages. However, it is not yet known whether TF expression has any functional significance in TB pathogenesis. In the present study, we investigated the role of TF in M.tb-induced inflammatory responses, mycobacterial growth and containment of infection. Wild-type C57BL6 (WT) and transgenic mice that express either very low levels of human TF (low TF, ~1% of WT) or high levels of human TF (HTF, ~100% of WT) in place of murine TF were infected with aerosol exposure of M.tb H37Rv. Mice were sacrificed 2 and 8 weeks post-infection. An evaluation of in vivo TF expression, coagulation activation, proinflammatory cytokines and tissue bacterial burden was performed. M.tb infection did not significantly alter overall TF expression and procoagulant activity in lungs of WT and HTF mice. Although not statistically significant, M.tb infection increased TF activity substantially in the lung homogenates in low TF mice. Nonetheless, TF expression levels in lungs of low TF mice, both uninfected and M.tb.-infected, was negligible as compared to WT and HTF mice. M.tb infection markedly increased TF expression in localized areas within the granulomas of WT and HTF mice. Interestingly, these intensely stained TF positive patches were also present in the granulomas of low TF mice after M.tb infection. The increased localized expression of TF in low TF mice may be responsible for the increased TF activity in the lung homogenates in low TF mice. M.tb infection was not accompanied by systemic and pulmonary activation of coagulation in WT and HTF mice. There was no change in the plasma thrombin-anti-thrombin complexes (TATc) upon M.tb infection in all three genotypes. Although, the bronchoalveolar lavage (BAL) TATc significantly increased (10-fold) after M.tb infection in the low TF mice, still the level was 15-50 folds lower than those in HTF and WT mice. The levels of TNF-α, IFN-γ, IL-6 and IL1-β increased upon M.tb infection but no significant differences in the cytokine profiles of BAL and total lung homogenates were observed among the genotypes. Higher expression of TF in the granuloma of WT and HTF correlated with the presence of small discrete regions of fibrin islands especially extending toward outer margin of the granuloma whereas little fibrin staining was seen in the granuloma of low TF mice. Despite, marked differences in fibrin generation in the granuloma, there were no significant differences in either lung bacterial burden or dissemination to liver and spleen. In summary, our data suggest that TF-mediated coagulation and/or signaling does not appear to contribute to host defense during experimental tuberculosis. However, it is difficult to completely eliminate a role for TF in M.tb. pathogenesis since M.tb. induced significant amount of TF expression in localized areas in the granuloma even in low TF mice. It is possible that this small amount of TF expressed within the granuloma may be sufficient to mediate local coagulant and signaling functions to facilitate M.tb. growth and dissemination. Disclosures No relevant conflicts of interest to declare.

The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs)

2018 ◽  
Vol 6 (6) ◽  
pp. 1556-1568 ◽  
Author(s):  
Xianfang Jiang ◽  
Xianyuan Huang ◽  
Tongmeng Jiang ◽  
Li Zheng ◽  
Jinmin Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Chondrogenic Differentiation ◽  
Collagen Hydrogel ◽  
Adult Mesenchymal Stem Cells

Sox9 is a transcription factor that regulates chondrogenesis, but its role in the chondrogenic differentiation of mesenchymal stem cells (MSCs) triggered by materials is poorly understood.

Overexpression of Pygo2 Increases Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Cardiomyocyte-like Cells

2020 ◽  
Vol 20 (4) ◽  
pp. 318-324 ◽  
Author(s):  
Lei Yang ◽  
Shuoji Zhu ◽  
Yongqing Li ◽  
Jian Zhuang ◽  
Jimei Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Heart Function ◽  
Critical Role ◽  
Human Umbilical Cord ◽  
Stem Cell Markers ◽  
Quantitative Real Time Pcr ◽  
Qrt Pcr

Background: Our previous studies have shown that Pygo (Pygopus) in Drosophila plays a critical role in adult heart function that is likely conserved in mammals. However, its role in the differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) into cardiomyocytes remains unknown. Objective: To investigate the role of pygo2 in the differentiation of hUC-MSCs into cardiomyocytes. Methods: Third passage hUC-MSCs were divided into two groups: a p+ group infected with the GV492-pygo2 virus and a p− group infected with the GV492 virus. After infection and 3 or 21 days of incubation, Quantitative real-time PCR (qRT-PCR) was performed to detect pluripotency markers, including OCT-4 and SOX2. Nkx2.5, Gata-4 and cTnT were detected by immunofluorescence at 7, 14 and 21 days post-infection, respectively. Expression of cardiac-related genes—including Nkx2.5, Gata-4, TNNT2, MEF2c, ISL-1, FOXH1, KDR, αMHC and α-Actin—were analyzed by qRT-PCR following transfection with the virus at one, two and three weeks. Results : After three days of incubation, there were no significant changes in the expression of the pluripotency stem cell markers OCT-4 and SOX2 in the p+ group hUC-MSCs relative to controls (OCT-4: 1.03 ± 0.096 VS 1, P > 0.05, SOX2: 1.071 ± 0.189 VS 1, P > 0.05); however, after 21 days, significant decreases were observed (OCT-4: 0.164 ± 0.098 VS 1, P < 0.01, SOX2: 0.209 ± 0.109 VS 1, P < 0.001). Seven days following incubation, expression of mesoderm specialisation markers, such as Nkx2.5, Gata-4, MEF2c and KDR, were increased; at 14 days following incubation, expression of cardiac genes, such as Nkx2.5, Gata-4, TNNT2, MEF2c, ISL-1, FOXH1, KDR, αMHC and α-Actin, were significantly upregulated in the p+ group relative to the p− group (P < 0.05). Taken together, these findings suggest that overexpression of pygo2 results in more hUCMSCs gradually differentiating into cardiomyocyte-like cells. Conclusion: We are the first to show that overexpression of pygo2 significantly enhances the expression of cardiac-genic genes, including Nkx2.5 and Gata-4, and promotes the differentiation of hUC-MSCs into cardiomyocyte-like cells.

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