The Experts below are selected from a list of 27090 Experts worldwide ranked by ideXlab platform
Chung Ming Chen - One of the best experts on this subject based on the ideXlab platform.
-
Consecutive daily administration of intratracheal surfactant and human umbilical cord-derived mesenchymal stem cells attenuates Hyperoxia-Induced Lung Injury in neonatal rats.
Stem cell research & therapy, 2021Co-Authors: Hsiu-chu Chou, Chien-hsiang Chang, Chien-han Chen, Willie Lin, Chung Ming ChenAbstract:Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated Hyperoxia-Induced Lung Injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on Hyperoxia-Induced Lung Injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on Hyperoxia-Induced Lung Injury. Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or hUC-MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + hUC-MSCs (3 × 104 cells), and O2 + surfactant + hUC-MSCs (3 × 105 cells). The Lungs were excised for histological, western blot, and cytokine analyses. The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1β and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 104 cells) treatment attenuated Hyperoxia-Induced Lung Injury. The surfactant + hUC-MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 104 cells) group did. Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating Hyperoxia-Induced Lung Injury in neonates.
-
Consecutive Daily Administration of Intratracheal Surfactant and Human Mesenchymal Stem Cells Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats
2021Co-Authors: Hsiu-chu Chou, Chien-hsiang Chang, Chien-han Chen, Willie Lin, Chung Ming ChenAbstract:Abstract Background: Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Mesenchymal stem cells (MSCs) attenuated Hyperoxia-Induced Lung Injury. Surfactant reduced the in vitro viability of human MSCs, and the combination therapy of surfactant and MSCs did not have additive effects on Hyperoxia-Induced Lung Injury in neonatal rats. The effects of 2 consecutive days of intratracheal administration of surfactant and MSCs on Hyperoxia-Induced Lung Injury were undetermined. Methods: Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or human MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + MSCs (3 × 104 cells), and O2 + surfactant + MSCs (3 × 105 cells). The Lungs were excised for analysis on postnatal day 14.Results: The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and cytokine levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokine levels and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + MSCs (3 × 104 cells) treatment attenuated Hyperoxia-Induced Lung Injury. The surfactant + MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + MSCs (3 × 104 cells) group did.Conclusions: Consecutive daily administration of intratracheal surfactant and MSCs can be an effective regimen for treating Hyperoxia-Induced Lung Injury in neonates.
-
Maternal antibiotic exposure disrupts microbiota and exacerbates Hyperoxia-Induced Lung Injury in neonatal mice
Pediatric Research, 2021Co-Authors: Chung Ming Chen, Yu-chen S. H. Yang, Hsiu-chu ChouAbstract:Background Perinatal antibiotic treatment alters intestinal microbiota and augments Hyperoxia-Induced Lung Injury in mice offspring. The effect of maternal antibiotic treatment (MAT) during pregnancy on the Lung microbiota and its relationship with Lung Injury remains unknown. Methods We fed timed-pregnant C57BL/6N mice sterile drinking water containing antibiotics from gestational day 15 to delivery. Neonatal mice were reared in either room air (RA) or hyperoxia (85% O_2) from postnatal days 1 to 7. Four study groups were obtained: control + RA, control + O_2, MAT + RA, and MAT + O_2. On postnatal day 7, Lung and intestinal microbiota were sampled from the left Lung and lower gastrointestinal tract. The right Lung was harvested for histology and cytokine analysis. Results MAT during pregnancy significantly reduced the total number of commensal bacteria in the intestine and birth body weight of newborn mice compared with control newborn mice. Neonatal hyperoxia exposure impaired alveolarization and angiogenesis, which was exacerbated by MAT. Neonatal hyperoxia altered the composition and diversity of intestinal and Lung microbiota and MAT further exacerbated neonatal Hyperoxia-Induced intestinal and Lung dysbiosis. Conclusions MAT during pregnancy exacerbates Hyperoxia-Induced Lung Injury probably through the modulation of intestinal and Lung microbiota in neonatal mice. Impact MAT during pregnancy reduced the total number of commensal bacteria in the intestine. Neonatal hyperoxia altered the composition and diversity of intestinal and Lung microbiota. MAT exacerbated neonatal Hyperoxia-Induced intestinal and Lung dysbiosis. Neonatal hyperoxia exposure impaired alveolarization and angiogenesis, which was exacerbated by MAT. Avoiding and carefully using antibiotics during pregnancy is a potential therapeutic target for preventing Lung Injury in hyperoxia-exposed infants.
-
Anti-Tn Monoclonal Antibody Attenuates Hyperoxia-Induced Lung Injury by Inhibiting Oxidative Stress and Inflammation in Neonatal Mice.
Frontiers in pharmacology, 2020Co-Authors: Chung Ming Chen, Hsiu-chu Chou, Jaulang Hwang, Chinde ChenAbstract:Maternal immunization with Tn vaccine increases serum anti-Tn antibody titers and attenuates Hyperoxia-Induced Lung Injury in neonatal rats. This study determined whether anti-Tn monoclonal antibody can protect against Hyperoxia-Induced Lung Injury in neonatal mice. Newborn BALB/c mice were exposed to room air (RA) or normobaric hyperoxia (85% O2) for 1 week, creating four study groups as follows: RA + phosphate-buffered saline (PBS), RA + anti-Tn monoclonal antibody, O2 + PBS, and O2 + anti-Tn monoclonal antibody. The anti-Tn monoclonal antibody at 25 μg/g body weight in 50 μl PBS was intraperitoneally injected on postnatal days 2, 4, and 6. Hyperoxia reduced body weight and survival rate, increased mean linear intercept (MLI) and Lung tumor necrosis factor-α, and decreased vascular endothelial growth factor (VEGF) expression and vascular density on postnatal day 7. Anti-Tn monoclonal antibody increased neonatal serum anti-Tn antibody titers, reduced MLI and cytokine, and increased VEGF expression and vascular density to normoxic levels. The attenuation of Lung Injury was accompanied by a reduction in Lung oxidative stress and nuclear factor-κB activity. Anti-Tn monoclonal antibody improves alveolarization and angiogenesis in hyperoxia-injured newborn mice Lungs through the suppression of oxidative stress and inflammation.
-
Predicting Hyperoxia-Induced Lung Injury from Associated Intestinal and Lung Dysbiosis in Neonatal Mice
2020Co-Authors: Chung Ming Chen, Hsiu-chu Chou, Yu-chen YangAbstract:Abstract Background: Newborns with respiratory disorders often require supplemental oxygen. Preclinical studies have demonstrated that hyperoxia disrupts the intestinal barrier, impairs intestinal function, and injures the Lungs of newborn animals. The effects of neonatal hyperoxia on intestinal and Lung microbiota and the role of the intestinal microbiota in the pathogenesis of Hyperoxia-Induced Lung Injury have not been investigated.Results: In this study, we evaluated the effect of neonatal hyperoxia on intestine and Lung microbiota alterations in neonatal C57BL/6N mice reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 7. On postnatal day 7, Lung and intestinal microbiota were sampled from the left Lung and lower gastrointestinal tract for 16S ribosomal RNA gene sequencing. Tissue from the right Lung and terminal ileum were harvested for Western blot and histology analysis. Hyperoxia decreased body weight, induced intestinal Injury, decreased intestinal tight junction expression, impaired Lung alveolarization and angiogenesis, and increased Lung cytokines in neonatal mice. Hyperoxia also altered intestinal and Lung microbiota and promoted bacterial translocation from the intestine to the Lung as evidenced by the presence of intestinal bacteria in the Lungs of hyperoxia-exposed neonatal mice. The relative abundance of these bacterial taxa was significantly positively correlated with Lung cytokines. Intestinal and Lung microbiota combined with cytokines were incorporated into machine learning algorithms to develop prediction models for the classification of RA- or hyperoxia-reared mice. The experiment results demonstrated that a Bayes network achieved the best predictive performance, attaining accuracy, sensitivity, specificity, and area under the curve values of 94.4%, 88.9%, 100%, and 0.963, respectively. Selected discriminative features included Lung cytokines (interleukin-1β, macrophage inflammatory protein-2, and tumor necrosis factor-α), Lung microbiota (Ruminococcaceae_UCG-010, CAG-56, and Enterobacter), and intestinal microbiota (Peptococcaceae_ge, Muribaculum, Enterobacter, and Ruminococcaceae_UCG-010). Conclusions: Neonatal hyperoxia exposure during the first week of life induced intestinal and Lung dysbiosis and promoted bacterial translocation from the intestine to the Lung. These findings suggest that changes in the composition of the intestinal microbiota contribute to Hyperoxia-Induced Lung Injury and that the combination of intestinal and Lung microbiota may indicate Hyperoxia-Induced Lung Injury in neonatal mice.
Hsiu-chu Chou - One of the best experts on this subject based on the ideXlab platform.
-
Consecutive daily administration of intratracheal surfactant and human umbilical cord-derived mesenchymal stem cells attenuates Hyperoxia-Induced Lung Injury in neonatal rats.
Stem cell research & therapy, 2021Co-Authors: Hsiu-chu Chou, Chien-hsiang Chang, Chien-han Chen, Willie Lin, Chung Ming ChenAbstract:Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated Hyperoxia-Induced Lung Injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on Hyperoxia-Induced Lung Injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on Hyperoxia-Induced Lung Injury. Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or hUC-MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + hUC-MSCs (3 × 104 cells), and O2 + surfactant + hUC-MSCs (3 × 105 cells). The Lungs were excised for histological, western blot, and cytokine analyses. The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1β and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 104 cells) treatment attenuated Hyperoxia-Induced Lung Injury. The surfactant + hUC-MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 104 cells) group did. Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating Hyperoxia-Induced Lung Injury in neonates.
-
Consecutive Daily Administration of Intratracheal Surfactant and Human Mesenchymal Stem Cells Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats
2021Co-Authors: Hsiu-chu Chou, Chien-hsiang Chang, Chien-han Chen, Willie Lin, Chung Ming ChenAbstract:Abstract Background: Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Mesenchymal stem cells (MSCs) attenuated Hyperoxia-Induced Lung Injury. Surfactant reduced the in vitro viability of human MSCs, and the combination therapy of surfactant and MSCs did not have additive effects on Hyperoxia-Induced Lung Injury in neonatal rats. The effects of 2 consecutive days of intratracheal administration of surfactant and MSCs on Hyperoxia-Induced Lung Injury were undetermined. Methods: Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or human MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + MSCs (3 × 104 cells), and O2 + surfactant + MSCs (3 × 105 cells). The Lungs were excised for analysis on postnatal day 14.Results: The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and cytokine levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokine levels and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + MSCs (3 × 104 cells) treatment attenuated Hyperoxia-Induced Lung Injury. The surfactant + MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + MSCs (3 × 104 cells) group did.Conclusions: Consecutive daily administration of intratracheal surfactant and MSCs can be an effective regimen for treating Hyperoxia-Induced Lung Injury in neonates.
-
Maternal antibiotic exposure disrupts microbiota and exacerbates Hyperoxia-Induced Lung Injury in neonatal mice
Pediatric Research, 2021Co-Authors: Chung Ming Chen, Yu-chen S. H. Yang, Hsiu-chu ChouAbstract:Background Perinatal antibiotic treatment alters intestinal microbiota and augments Hyperoxia-Induced Lung Injury in mice offspring. The effect of maternal antibiotic treatment (MAT) during pregnancy on the Lung microbiota and its relationship with Lung Injury remains unknown. Methods We fed timed-pregnant C57BL/6N mice sterile drinking water containing antibiotics from gestational day 15 to delivery. Neonatal mice were reared in either room air (RA) or hyperoxia (85% O_2) from postnatal days 1 to 7. Four study groups were obtained: control + RA, control + O_2, MAT + RA, and MAT + O_2. On postnatal day 7, Lung and intestinal microbiota were sampled from the left Lung and lower gastrointestinal tract. The right Lung was harvested for histology and cytokine analysis. Results MAT during pregnancy significantly reduced the total number of commensal bacteria in the intestine and birth body weight of newborn mice compared with control newborn mice. Neonatal hyperoxia exposure impaired alveolarization and angiogenesis, which was exacerbated by MAT. Neonatal hyperoxia altered the composition and diversity of intestinal and Lung microbiota and MAT further exacerbated neonatal Hyperoxia-Induced intestinal and Lung dysbiosis. Conclusions MAT during pregnancy exacerbates Hyperoxia-Induced Lung Injury probably through the modulation of intestinal and Lung microbiota in neonatal mice. Impact MAT during pregnancy reduced the total number of commensal bacteria in the intestine. Neonatal hyperoxia altered the composition and diversity of intestinal and Lung microbiota. MAT exacerbated neonatal Hyperoxia-Induced intestinal and Lung dysbiosis. Neonatal hyperoxia exposure impaired alveolarization and angiogenesis, which was exacerbated by MAT. Avoiding and carefully using antibiotics during pregnancy is a potential therapeutic target for preventing Lung Injury in hyperoxia-exposed infants.
-
Anti-Tn Monoclonal Antibody Attenuates Hyperoxia-Induced Lung Injury by Inhibiting Oxidative Stress and Inflammation in Neonatal Mice.
Frontiers in pharmacology, 2020Co-Authors: Chung Ming Chen, Hsiu-chu Chou, Jaulang Hwang, Chinde ChenAbstract:Maternal immunization with Tn vaccine increases serum anti-Tn antibody titers and attenuates Hyperoxia-Induced Lung Injury in neonatal rats. This study determined whether anti-Tn monoclonal antibody can protect against Hyperoxia-Induced Lung Injury in neonatal mice. Newborn BALB/c mice were exposed to room air (RA) or normobaric hyperoxia (85% O2) for 1 week, creating four study groups as follows: RA + phosphate-buffered saline (PBS), RA + anti-Tn monoclonal antibody, O2 + PBS, and O2 + anti-Tn monoclonal antibody. The anti-Tn monoclonal antibody at 25 μg/g body weight in 50 μl PBS was intraperitoneally injected on postnatal days 2, 4, and 6. Hyperoxia reduced body weight and survival rate, increased mean linear intercept (MLI) and Lung tumor necrosis factor-α, and decreased vascular endothelial growth factor (VEGF) expression and vascular density on postnatal day 7. Anti-Tn monoclonal antibody increased neonatal serum anti-Tn antibody titers, reduced MLI and cytokine, and increased VEGF expression and vascular density to normoxic levels. The attenuation of Lung Injury was accompanied by a reduction in Lung oxidative stress and nuclear factor-κB activity. Anti-Tn monoclonal antibody improves alveolarization and angiogenesis in hyperoxia-injured newborn mice Lungs through the suppression of oxidative stress and inflammation.
-
Predicting Hyperoxia-Induced Lung Injury from Associated Intestinal and Lung Dysbiosis in Neonatal Mice
2020Co-Authors: Chung Ming Chen, Hsiu-chu Chou, Yu-chen YangAbstract:Abstract Background: Newborns with respiratory disorders often require supplemental oxygen. Preclinical studies have demonstrated that hyperoxia disrupts the intestinal barrier, impairs intestinal function, and injures the Lungs of newborn animals. The effects of neonatal hyperoxia on intestinal and Lung microbiota and the role of the intestinal microbiota in the pathogenesis of Hyperoxia-Induced Lung Injury have not been investigated.Results: In this study, we evaluated the effect of neonatal hyperoxia on intestine and Lung microbiota alterations in neonatal C57BL/6N mice reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 7. On postnatal day 7, Lung and intestinal microbiota were sampled from the left Lung and lower gastrointestinal tract for 16S ribosomal RNA gene sequencing. Tissue from the right Lung and terminal ileum were harvested for Western blot and histology analysis. Hyperoxia decreased body weight, induced intestinal Injury, decreased intestinal tight junction expression, impaired Lung alveolarization and angiogenesis, and increased Lung cytokines in neonatal mice. Hyperoxia also altered intestinal and Lung microbiota and promoted bacterial translocation from the intestine to the Lung as evidenced by the presence of intestinal bacteria in the Lungs of hyperoxia-exposed neonatal mice. The relative abundance of these bacterial taxa was significantly positively correlated with Lung cytokines. Intestinal and Lung microbiota combined with cytokines were incorporated into machine learning algorithms to develop prediction models for the classification of RA- or hyperoxia-reared mice. The experiment results demonstrated that a Bayes network achieved the best predictive performance, attaining accuracy, sensitivity, specificity, and area under the curve values of 94.4%, 88.9%, 100%, and 0.963, respectively. Selected discriminative features included Lung cytokines (interleukin-1β, macrophage inflammatory protein-2, and tumor necrosis factor-α), Lung microbiota (Ruminococcaceae_UCG-010, CAG-56, and Enterobacter), and intestinal microbiota (Peptococcaceae_ge, Muribaculum, Enterobacter, and Ruminococcaceae_UCG-010). Conclusions: Neonatal hyperoxia exposure during the first week of life induced intestinal and Lung dysbiosis and promoted bacterial translocation from the intestine to the Lung. These findings suggest that changes in the composition of the intestinal microbiota contribute to Hyperoxia-Induced Lung Injury and that the combination of intestinal and Lung microbiota may indicate Hyperoxia-Induced Lung Injury in neonatal mice.
Cleide Suguihara - One of the best experts on this subject based on the ideXlab platform.
-
Stem cell factor improves Lung recovery in rats following neonatal Hyperoxia-Induced Lung Injury
Pediatric research, 2013Co-Authors: Luis F. Miranda, Claudia O. Rodrigues, Shalini Ramachandran, Eneida Torres, Jian Huang, Jammie Klim, Dorothy Hehre, Ian Mcniece, Joshua M. Hare, Cleide SuguiharaAbstract:Stem cell factor improves Lung recovery in rats following neonatal Hyperoxia-Induced Lung Injury
-
long term reparative effects of mesenchymal stem cell therapy following neonatal hyperoxia induced Lung Injury
Pediatric Research, 2013Co-Authors: Ronald P Sutsko, Eneida Torres, Dorothy Hehre, Ian Mcniece, Karen C Young, Ana Ribeiro, Myra Rodriguez, Carlos Devia, Cleide SuguiharaAbstract:Long-term reparative effects of mesenchymal stem cell therapy following neonatal Hyperoxia-Induced Lung Injury
-
Long-term reparative effects of mesenchymal stem cell therapy following neonatal Hyperoxia-Induced Lung Injury
Pediatric Research, 2013Co-Authors: Ronald P Sutsko, Eneida Torres, Dorothy Hehre, Ian Mcniece, Karen C Young, Ana Ribeiro, Myra Rodriguez, Carlos Devia, Cleide SuguiharaAbstract:Background: Mesenchymal stem cell (MSC) therapy may prevent neonatal Hyperoxia-Induced Lung Injury (HILI). There are, however, no clear data on the therapeutic efficacy of MSC therapy in established HILI, the duration of the reparative effects, and the exact mechanisms of repair. The main objective of this study was to evaluate whether the long-term reparative effects of a single intratracheal (IT) dose of MSCs or MSC-conditioned medium (CM) are comparable in established HILI. Methods: Newborn rats exposed to normoxia or hyperoxia from postnatal day (P)2)–P16 were randomized to receive IT MSCs, IT CM, or IT placebo (PL) on P9. Alveolarization and angiogenesis were evaluated at P16, P30, and P100. Results: At all time periods, there were marked improvements in alveolar and vascular development in hyperoxic pups treated with MSCs or CM as compared with PL. This was associated with decreased expression of inflammatory mediators and an upregulation of angiogenic factors. Of note, at P100, the improvements were more substantial with MSCs as compared with CM. Conclusion: These data suggest that acute effects of MSC therapy in HILI are mainly paracrine mediated; however, optimum long-term improvement following HILI requires treatment with the MSCs themselves or potentially repetitive administration of CM.
Dorothy Hehre - One of the best experts on this subject based on the ideXlab platform.
-
Stem cell factor improves Lung recovery in rats following neonatal Hyperoxia-Induced Lung Injury
Pediatric research, 2013Co-Authors: Luis F. Miranda, Claudia O. Rodrigues, Shalini Ramachandran, Eneida Torres, Jian Huang, Jammie Klim, Dorothy Hehre, Ian Mcniece, Joshua M. Hare, Cleide SuguiharaAbstract:Stem cell factor improves Lung recovery in rats following neonatal Hyperoxia-Induced Lung Injury
-
long term reparative effects of mesenchymal stem cell therapy following neonatal hyperoxia induced Lung Injury
Pediatric Research, 2013Co-Authors: Ronald P Sutsko, Eneida Torres, Dorothy Hehre, Ian Mcniece, Karen C Young, Ana Ribeiro, Myra Rodriguez, Carlos Devia, Cleide SuguiharaAbstract:Long-term reparative effects of mesenchymal stem cell therapy following neonatal Hyperoxia-Induced Lung Injury
-
Long-term reparative effects of mesenchymal stem cell therapy following neonatal Hyperoxia-Induced Lung Injury
Pediatric Research, 2013Co-Authors: Ronald P Sutsko, Eneida Torres, Dorothy Hehre, Ian Mcniece, Karen C Young, Ana Ribeiro, Myra Rodriguez, Carlos Devia, Cleide SuguiharaAbstract:Background: Mesenchymal stem cell (MSC) therapy may prevent neonatal Hyperoxia-Induced Lung Injury (HILI). There are, however, no clear data on the therapeutic efficacy of MSC therapy in established HILI, the duration of the reparative effects, and the exact mechanisms of repair. The main objective of this study was to evaluate whether the long-term reparative effects of a single intratracheal (IT) dose of MSCs or MSC-conditioned medium (CM) are comparable in established HILI. Methods: Newborn rats exposed to normoxia or hyperoxia from postnatal day (P)2)–P16 were randomized to receive IT MSCs, IT CM, or IT placebo (PL) on P9. Alveolarization and angiogenesis were evaluated at P16, P30, and P100. Results: At all time periods, there were marked improvements in alveolar and vascular development in hyperoxic pups treated with MSCs or CM as compared with PL. This was associated with decreased expression of inflammatory mediators and an upregulation of angiogenic factors. Of note, at P100, the improvements were more substantial with MSCs as compared with CM. Conclusion: These data suggest that acute effects of MSC therapy in HILI are mainly paracrine mediated; however, optimum long-term improvement following HILI requires treatment with the MSCs themselves or potentially repetitive administration of CM.
-
Connective tissue growth factor antibody therapy attenuates Hyperoxia-Induced Lung Injury in neonatal rats.
American journal of respiratory cell and molecular biology, 2011Co-Authors: Deepthi Alapati, Dorothy Hehre, Min Rong, Shaoyi Chen, Maria M. Rodriguez, Kenneth E. LipsonAbstract:Despite recent advances in neonatal intensive care and surfactant therapy, bronchopulmonary dysplasia (BPD) continues to be one of the most common long-term pulmonary complications associated with preterm birth. Clinical efforts to prevent and treat BPD have been largely unsuccessful due to its multifactorial nature and poorly understood disease process. Connective tissue growth factor (CTGF) is a matricellular protein that plays an important role in tissue development and remodeling. Previous studies have demonstrated that hyperoxia exposure up-regulates CTGF expression in neonatal rat Lungs. Whether CTGF overexpression plays a role in the pathogenesis of BPD, and whether CTGF antagonism has a therapeutic potential for BPD, are unknown. In the present study, we examined CTGF expression in Lung autopsy specimens from patients with BPD and control subjects with no BPD. We assessed the effect of a CTGF-neutralizing monoclonal antibody (CTGF Ab) on preventing Hyperoxia-Induced Lung Injury in neonatal rats. O...
Won Soon Park - One of the best experts on this subject based on the ideXlab platform.
-
Antenatal betamethasone attenuates intrauterine infection-aggravated Hyperoxia-Induced Lung Injury in neonatal rats
Pediatric research, 2013Co-Authors: Hye Soo Yoo, Yun Sil Chang, Jin Kyu Kim, So Yoon Ahn, Eun Sun Kim, Dong Kyung Sung, Ga Won Jeon, Jong Hee Hwang, Jae Won Shim, Won Soon ParkAbstract:Antenatal betamethasone attenuates intrauterine infection-aggravated Hyperoxia-Induced Lung Injury in neonatal rats
-
Granulocyte colony stimulating factor attenuates Hyperoxia-Induced Lung Injury by down-modulating inflammatory responses in neonatal rats.
Yonsei medical journal, 2011Co-Authors: Ga Won Jeon, Yun Sil Chang, Dong Kyung Sung, Soo Hyun Koo, Yu Jin Jung, Seo Heui Choi, Jong Beom Sin, Won Soon ParkAbstract:PURPOSE: Granulocyte colony stimulating factor (G-CSF) has been known to increase neutrophil production and have anti-inflammatory properties, but the effect of G-CSF on pulmonary system is in controversy. We investigated whether G-CSF treatment could attenuate Hyperoxia-Induced Lung Injury, and whether this protective effect is mediated by the down-modulation of inflammatory responses in a neonatal rat model. MATERIALS AND METHODS: Newborn Sprague-Dawley rats (Orient Co., Seoul, Korea) were subjected to 14 days of hyperoxia (90% oxygen) beginning within 10 h after birth. G-CSF (20 μg/kg) was administered intraperitoneally on the fourth, fifth, and sixth postnatal days. RESULTS: This treatment significantly improved Hyperoxia-Induced reduction in body weight gain and Lung pathology such as increased mean linear intercept, mean alveolar volume, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling positive cells. Hyperoxia- induced activation of nicotinamide adenine dinucleotide phosphate oxidase, which is responsible for superoxide anion production, as evidenced by upregulation and membrane translocation of p67(phox) was significantly attenuated after G-CSF treatment, as were inflammatory responses such as increased myeloperoxidase activity and mRNA expression of transforming growth factor-β. However, the attenuation of other proinflammatory cytokines such as tumor necrosis factor-α and interleukin- 6 was not significant. CONCLUSION: In sum, G-CSF treatment significantly attenuated Hyperoxia-Induced Lung Injury by down-modulating the inflammatory responses in neonatal rats.
-
α-PHENYL-N-tert-BUTYLNITRONE ATTENUATES Hyperoxia-Induced Lung Injury BY DOWN-MODULATING INFLAMMATION IN NEONATAL RATS
Experimental lung research, 2009Co-Authors: Yun Sil Chang, Hye Soo Yoo, Dong Kyung Sung, Yu Jin Kim, Soo Yoon Kim, Saem Kang, Won Soon ParkAbstract:This study was done to determine whether alpha -phenyl-N-tert-butylnitrone (PBN), a spin-trapping agent possessing significant anti-inflammatory capabilities, could attenuate Hyperoxia-Induced Lung Injury, and if so, whether this protective effect is mediated by the down-modulation of inflammation in neonatal rats. Newborn Sprague-Dawley rat pups were subjected to 14 days of hyperoxia (> 90% oxygen) within 10 hours after birth. PBN treatment, given 100 mg/kg intraperitoneally daily throughout the experiment, significantly attenuated Hyperoxia-Induced Lung pathology, such as decreased radial alveolar count, increased mean linear intercept, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive cells. Hyperoxia-Induced activation of nicotinamide adenine dinucleotide phosphate oxidase that is responsible for superoxide anion production, as evidenced by up-regulation and membrane translocation of p67phox, and the inflammatory responses, such as increased mRNA expression of tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta, were also significantly attenuated with PBN treatment. In summary, a spin-trapping agent PBN significantly attenuated Hyperoxia-Induced Lung Injury by down-regulating the inflammatory responses in neonatal rats.
-
Human umbilical cord blood-derived mesenchymal stem cells attenuate Hyperoxia-Induced Lung Injury in neonatal rats.
Cell transplantation, 2009Co-Authors: Yun Sil Chang, Dong Kyung Sung, Soo Yoon Kim, Saem Kang, Soo Jin Choi, Eun Yang Choi, Hye Jin Jin, Yoon Sun Yang, Won Soon ParkAbstract:Recent evidence suggests mesenchymal stem cells (MSCs) can downmodulate bleomycin-induced Lung Injury, and umbilical cord blood (UCB) is a promising source for human MSCs. This study examined whether intratracheal or intraperitoneal transplantation of human UCB-derived MSCs can attenuate Hyperoxia-Induced Lung Injury in immunocompetent newborn rats. Wild-type Sprague-Dawley rats were randomly exposed to 95% oxygen or air from birth. In the transplantation groups, a single dose of PKH26-labeled human UCB-derived MSCs was administered either intratracheally (2 x 10(6) cells) or intraperitoneally (5 x 10(5) cells) at postnatal day (P) 5. At P14, the harvested Lungs were examined for morphometric analyses of alveolarization and TUNEL staining, as well as the myeoloperoxidase activity, the level of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and transforming growth factor (TGF)-beta mRNA, alpha-smooth muscle actin (SMA) protein, and collagen levels. Differentiation of MSCs to the respiratory epithelium was also evaluated both in vitro before transplantation and in vivo after transplantation. Despite one fourth dosage of MSCs, significantly more PKH26-labeled donor cells were recovered with intratracheal administration than with intraperitoneal administration both during normoxia and hyperoxia. The Hyperoxia-Induced increase in the number of TUNEL-positive cells, myeloperoixdase activity, and the level of IL-6 mRNA were significantly attenuated with both intratracheal and intraperitoneal MSCs transplantation. However, the Hyperoxia-Induced impaired alveolarization and increased the level of TNF-alpha and TGF-beta mRNA, alpha-SMA protein, and collagen were significantly attenuated only with intratracheal MSCs transplantation. MSCs differentiated into respiratory epithelium in vitro and a few PKH26-positive donor cells were colocalized with pro surfactant protein C in the damaged Lungs. In conclusion, intratracheal transplantation of human UCB-derived MSCs is more effective than intraperitoneal transplantation in attenuating the Hyperoxia-Induced Lung Injury in neonatal rats.
-
Intratracheal Administration of Endotoxin Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats
Yonsei medical journal, 2008Co-Authors: Jae Won Shim, Yun Sil Chang, Won Soon ParkAbstract:Purpose: This study was undertaken to determine the effects of intratracheal administration of endotoxin on Hyperoxia-Induced Lung Injury in neonatal rats. Materials and Methods: Newborn Sprague Dawley rat pups were divided into four experimental groups: normoxia control (NC), normoxia with endotoxin treatment (NE), hyperoxia control (HC), and hyperoxia with endotoxin treatment (HE) groups. In HC and HE, rat pups were subjected to 14 days of hyperoxia (> 95% oxygen) within 12 hours after birth. In endotoxin treated group (NE and HE), Escherichia coli endotoxin (0.5 g in 0.03 μ mL of saline) was given intratracheally at the 1st, 3rd and 5th postnatal day. Radial alveolar count (RAC), mean linear intercept (MLI), RAC/MLI ratios, and degree of fibrosis were measured to assess the changes in Lung morphology. Results: During the research period, survival rates in both HC and HE were notably reduced 7 days after endotoxin was administered, but body weight gain was considerably reduced only in HC. On day 14, significant arrest in alveolarization, as evidenced by the decrease of RAC and RAC/MLI ratio and increase of MLI as well as increased fibrosis, were noted in HC. Although slight but significant arrest in alveolarization and increased fibrosis score were observed in NE compared to NC, the Hyperoxia-Induced Lung damage observed in HC was significantly improved in HE. Conclusion: This study suggests that intratracheal administration of endotoxin significantly attenuated Hyperoxia-Induced Lung Injury in neonatal rats.