The Experts below are selected from a list of 24774 Experts worldwide ranked by ideXlab platform
Dingyun Song - One of the best experts on this subject based on the ideXlab platform.
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immunity and matrix regulatory cells derived from human embryonic stem cells safely and effectively treat mouse Lung injury and fibrosis
Cell Research, 2020Co-Authors: Chunjing Feng, Dingyun Song, Baojie Guo, Yani Xiao, Wenjing Liu, Lingmin Liang, Tingting Gao, Yanxia Chen, Zai WangAbstract:Lung injury and fibrosis represent the most significant outcomes of severe and acute Lung Disorders, including COVID-19. However, there are still no effective drugs to treat Lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) produced under good manufacturing practice requirements, that can treat Lung injury and fibrosis in vivo. We generate IMRCs by sequentially differentiating hESCs with serum-free reagents. IMRCs possess a unique gene expression profile distinct from that of umbilical cord mesenchymal stem cells (UCMSCs), such as higher expression levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of Lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through paracrine regulatory mechanisms. IMRCs are superior to both primary UCMSCs and the FDA-approved drug pirfenidone, with an excellent efficacy and safety profile in mice and monkeys. In light of public health crises involving pneumonia, acute Lung injury and acute respiratory distress syndrome, our findings suggest that IMRCs are ready for clinical trials on Lung Disorders.
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immunity and matrix regulatory cells derived from human embryonic stem cells safely and effectively treat mouse Lung injury and fibrosis
bioRxiv, 2020Co-Authors: Dingyun Song, Chunjing Feng, Baojie Guo, Yani Xiao, Wenjing Liu, Lingmin Liang, Tingting Gao, Zai Wang, Jianyan Wen, Shengnan YangAbstract:Lung injury and fibrosis represent the most significant outcomes of severe and acute Lung Disorders, including COVID-19. However, there are still no effective drugs to treat Lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) manufactured under good manufacturing practice (GMP) requirements, that can treat Lung injury and fibrosis in vivo. We generate IMRCs through sequentially differentiating hESCs with xeno-free reagents. IMRCs possess a unique gene expression profile distinct from umbilical cord mesenchymal stem cells (UCMSCs), such as higher levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of Lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through their paracrine functions. IMRCs are superior to both primary UCMSCs and FDA-approved pirfenidone, with an excellent efficacy and safety profile in mice, monkeys and two severely ill COVID-19 patients in our pilot study. In light of recent public health crises involving pneumonia, acute Lung injury (ALI) and acute respiratory distress syndrome (ARDS), our findings indicate that IMRCs are ready for clinical trials on Lung Disorders.
Federica Genovese - One of the best experts on this subject based on the ideXlab platform.
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Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders
Elsevier, 2019Co-Authors: Signe Holm Nielsen, Nicholas Willumsen, Susanne Brix, Morten A. Karsdal, Federica Genovese, Diana Julie Leeming, Samuel Joseph Daniels, Mette Juul NielsenAbstract:OBJECTIVES: Remodeling of the extracellular matrix (ECM) is a key event in different Lung Disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-SMA, which has been found to be upregulated in Lung fibrosis and cancer. We evaluated the potential of α-SMA as a noninvasive biomarker of activated fibroblasts in Lung fibrosis and cancer. METHODS: A monoclonal antibody was raised against the N-terminal of α-SMA, and a novel competitive enzyme-linked immunosorbent assay (ELISA) measuring α-SMA was developed and technically characterized. Levels of α-SMA were measured in the fibroblast model, “scar-in-a-jar”, and in serum from patients with idiopathic pulmonary fibrosis (IPF), chronic obstructive Lung disorder (COPD) and non–small cell Lung cancer (NSCLC) belonging to two different cohorts. RESULTS: The novel α-SMA assay was developed and validated as technically robust. Based on the scar-in-a-jar results, α-SMA was only present in the fibroblasts activated by TGF-β. In cohort 1, levels of α-SMA were significantly higher in IPF, COPD and NSCLC patients compared to healthy controls (P = 0.04, P = 0.001 and P
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tumstatin a matrikine derived from collagen type ivα3 is elevated in serum from patients with non small cell Lung cancer
Translational Oncology, 2018Co-Authors: Signe Holm Nielsen, Nicholas Willumsen, Susanne Brix, Shu Sun, Morten A. Karsdal, Tina Manonjensen, Federica GenoveseAbstract:Abstract OBJECTIVES: Fibrosis and cancer are characterized by extracellular matrix (ECM) remodeling. The basement membrane is mainly composed by collagen type IV and laminin. Tumstatin is a matrix metalloproteinase-9 (MMP-9) generated matrikine of collagen type IV α3 chain. We evaluated the potential of tumstatin as a diagnostic biomarker of Lung Disorders. METHODS: A monoclonal antibody was raised against the neo-epitope tumstatin. A novel competitive enzyme-linked immunosorbent assay for detection of tumstatin (TUM), was developed and technically characterized. Levels of TUM were measured in serum of patients with idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and non–small cell Lung cancer (NSCLC) belonging to two cohorts. RESULTS: The developed TUM enzyme-linked immunosorbent assay (ELISA) was technically robust. In cohort 1, levels of TUM were significantly higher in NSCLC compared to healthy controls, IPF, and COPD ( P = 0.007, P = 0.03 and P = 0.001, respectively). The area under the receiver operating characteristics (AUROC) for separation of patients with NSCLC from healthy controls was 0.97, for separation of NSCLC and IPF patients was 0.98, and for separation of NSCLC and COPD patients was 1.0. In cohort 2, levels of TUM were also significantly higher in patients with NSCLC compared to healthy controls ( P = 0.002), and the AUROC for separation of NSCLC and healthy controls was 0.73. CONCLUSIONS: We developed a technically robust competitive ELISA targeting the fragment tumstatin. The level of TUM in circulation was significantly higher in patients with NSCLC compared to patients with IPF, COPD and healthy controls. The assay provided high diagnostic accuracy in separating NSCLC patients from other Lung Disorders and from healthy controls.
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Tumstatin, a Matrikine Derived from Collagen Type IVα3, is Elevated in Serum from Patients with Non–Small Cell Lung Cancer
Translational oncology, 2018Co-Authors: Signe Holm Nielsen, Nicholas Willumsen, Susanne Brix, Shu Sun, Tina Manon-jensen, Morten A. Karsdal, Federica GenoveseAbstract:Abstract OBJECTIVES: Fibrosis and cancer are characterized by extracellular matrix (ECM) remodeling. The basement membrane is mainly composed by collagen type IV and laminin. Tumstatin is a matrix metalloproteinase-9 (MMP-9) generated matrikine of collagen type IV α3 chain. We evaluated the potential of tumstatin as a diagnostic biomarker of Lung Disorders. METHODS: A monoclonal antibody was raised against the neo-epitope tumstatin. A novel competitive enzyme-linked immunosorbent assay for detection of tumstatin (TUM), was developed and technically characterized. Levels of TUM were measured in serum of patients with idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and non–small cell Lung cancer (NSCLC) belonging to two cohorts. RESULTS: The developed TUM enzyme-linked immunosorbent assay (ELISA) was technically robust. In cohort 1, levels of TUM were significantly higher in NSCLC compared to healthy controls, IPF, and COPD ( P = 0.007, P = 0.03 and P = 0.001, respectively). The area under the receiver operating characteristics (AUROC) for separation of patients with NSCLC from healthy controls was 0.97, for separation of NSCLC and IPF patients was 0.98, and for separation of NSCLC and COPD patients was 1.0. In cohort 2, levels of TUM were also significantly higher in patients with NSCLC compared to healthy controls ( P = 0.002), and the AUROC for separation of NSCLC and healthy controls was 0.73. CONCLUSIONS: We developed a technically robust competitive ELISA targeting the fragment tumstatin. The level of TUM in circulation was significantly higher in patients with NSCLC compared to patients with IPF, COPD and healthy controls. The assay provided high diagnostic accuracy in separating NSCLC patients from other Lung Disorders and from healthy controls.
Augustine M K Choi - One of the best experts on this subject based on the ideXlab platform.
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heme oxygenase colors of defense against cellular stress
American Journal of Physiology-lung Cellular and Molecular Physiology, 2000Co-Authors: Leo E Otterbein, Augustine M K ChoiAbstract:The discovery of the gaseous molecule nitric oxide in 1987 unraveled investigations on its functional role in the pathogenesis of a wide spectrum of biological and pathological processes. At that time, the novel concept that an endogenous production of a gaseous substance such as nitric oxide can impart such diverse and potent cellular effects proved to be very fruitful in enhancing our understanding of many disease processes including Lung Disorders. Interestingly, we have known for a longer period of time that there exists another gaseous molecule that is also generated endogenously; the heme oxygenase (HO) enzyme system generates the majority if not all of the endogenously produced carbon monoxide. This enzyme system also liberates two other by-products, bilirubin and ferritin, each possessing important biological functions and helping to define the uniqueness of the HO enzyme system. In recent years, interest in HO has emerged in numerous disciplines including the central nervous system, cardiovascula...
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heme oxygenase colors of defense against cellular stress
American Journal of Physiology-lung Cellular and Molecular Physiology, 2000Co-Authors: Leo E Otterbein, Augustine M K ChoiAbstract:The discovery of the gaseous molecule nitric oxide in 1987 unraveled investigations on its functional role in the pathogenesis of a wide spectrum of biological and pathological processes. At that time, the novel concept that an endogenous production of a gaseous substance such as nitric oxide can impart such diverse and potent cellular effects proved to be very fruitful in enhancing our understanding of many disease processes including Lung Disorders. Interestingly, we have known for a longer period of time that there exists another gaseous molecule that is also generated endogenously; the heme oxygenase (HO) enzyme system generates the majority if not all of the endogenously produced carbon monoxide. This enzyme system also liberates two other by-products, bilirubin and ferritin, each possessing important biological functions and helping to define the uniqueness of the HO enzyme system. In recent years, interest in HO has emerged in numerous disciplines including the central nervous system, cardiovascular physiology, renal and hepatic systems, and transplantation. We review the functional role of HO in Lung biology and its real potential application to Lung diseases.
Diederik Gommers - One of the best experts on this subject based on the ideXlab platform.
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bedside measurement of changes in Lung impedance to monitor alveolar ventilation in dependent and non dependent parts by electrical impedance tomography during a positive end expiratory pressure trial in mechanically ventilated intensive care unit patients
Critical Care, 2010Co-Authors: Ido G Bikker, Steffen Leonhardt, Dinis Reis Miranda, Jan Bakker, Diederik GommersAbstract:As it becomes clear that mechanical ventilation can exaggerate Lung injury, individual titration of ventilator settings is of special interest. Electrical impedance tomography (EIT) has been proposed as a bedside, regional monitoring tool to guide these settings. In the present study we evaluate the use of ventilation distribution change maps (ΔfEIT maps) in intensive care unit (ICU) patients with or without Lung Disorders during a standardized decremental positive end-expiratory pressure (PEEP) trial. Functional EIT (fEIT) images and PaO2/FiO2 ratios were obtained at four PEEP levels (15 to 10 to 5 to 0 cm H2O) in 14 ICU patients with or without Lung Disorders. Patients were pressure-controlled ventilated with constant driving pressure. fEIT images made before each reduction in PEEP were subtracted from those recorded after each PEEP step to evaluate regional increase/decrease in tidal impedance in each EIT pixel (ΔfEIT maps). The response of regional tidal impedance to PEEP showed a significant difference from 15 to 10 (P = 0.002) and from 10 to 5 (P = 0.001) between patients with and without Lung Disorders. Tidal impedance increased only in the non-dependent parts in patients without Lung Disorders after decreasing PEEP from 15 to 10 cm H2O, whereas it decreased at the other PEEP steps in both groups. During a decremental PEEP trial in ICU patients, EIT measurements performed just above the diaphragm clearly visualize improvement and loss of ventilation in dependent and non-dependent parts, at the bedside in the individual patient.
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bedside measurement of changes in Lung impedance to monitor alveolar ventilation in dependent and non dependent parts by electrical impedance tomography during a positive end expiratory pressure trial in mechanically ventilated intensive care unit patients
Critical Care, 2010Co-Authors: Ido G Bikker, Steffen Leonhardt, Dinis Reis Miranda, Jan Bakker, Diederik GommersAbstract:Introduction As it becomes clear that mechanical ventilation can exaggerate Lung injury, individual titration of ventilator settings is of special interest. Electrical impedance tomography (EIT) has been proposed as a bedside, regional monitoring tool to guide these settings. In the present study we evaluate the use of ventilation distribution change maps (ΔfEIT maps) in intensive care unit (ICU) patients with or without Lung Disorders during a standardized decremental positive end-expiratory pressure (PEEP) trial.
Zai Wang - One of the best experts on this subject based on the ideXlab platform.
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immunity and matrix regulatory cells derived from human embryonic stem cells safely and effectively treat mouse Lung injury and fibrosis
Cell Research, 2020Co-Authors: Chunjing Feng, Dingyun Song, Baojie Guo, Yani Xiao, Wenjing Liu, Lingmin Liang, Tingting Gao, Yanxia Chen, Zai WangAbstract:Lung injury and fibrosis represent the most significant outcomes of severe and acute Lung Disorders, including COVID-19. However, there are still no effective drugs to treat Lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) produced under good manufacturing practice requirements, that can treat Lung injury and fibrosis in vivo. We generate IMRCs by sequentially differentiating hESCs with serum-free reagents. IMRCs possess a unique gene expression profile distinct from that of umbilical cord mesenchymal stem cells (UCMSCs), such as higher expression levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of Lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through paracrine regulatory mechanisms. IMRCs are superior to both primary UCMSCs and the FDA-approved drug pirfenidone, with an excellent efficacy and safety profile in mice and monkeys. In light of public health crises involving pneumonia, acute Lung injury and acute respiratory distress syndrome, our findings suggest that IMRCs are ready for clinical trials on Lung Disorders.
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immunity and matrix regulatory cells derived from human embryonic stem cells safely and effectively treat mouse Lung injury and fibrosis
bioRxiv, 2020Co-Authors: Dingyun Song, Chunjing Feng, Baojie Guo, Yani Xiao, Wenjing Liu, Lingmin Liang, Tingting Gao, Zai Wang, Jianyan Wen, Shengnan YangAbstract:Lung injury and fibrosis represent the most significant outcomes of severe and acute Lung Disorders, including COVID-19. However, there are still no effective drugs to treat Lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) manufactured under good manufacturing practice (GMP) requirements, that can treat Lung injury and fibrosis in vivo. We generate IMRCs through sequentially differentiating hESCs with xeno-free reagents. IMRCs possess a unique gene expression profile distinct from umbilical cord mesenchymal stem cells (UCMSCs), such as higher levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of Lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through their paracrine functions. IMRCs are superior to both primary UCMSCs and FDA-approved pirfenidone, with an excellent efficacy and safety profile in mice, monkeys and two severely ill COVID-19 patients in our pilot study. In light of recent public health crises involving pneumonia, acute Lung injury (ALI) and acute respiratory distress syndrome (ARDS), our findings indicate that IMRCs are ready for clinical trials on Lung Disorders.
