Timing of erythropoietin modified mesenchymal stromal cell transplantation for the treatment of experimental bronchopulmonary dysplasia

Zhang, Zhaohua; Sun, Chao; Wang, Jue; Wen, Jiangqi; Xin, Qian; Luan, Yun

doi:10.1111/jcmm.13843

Cited by 12 publications

(8 citation statements)

References 14 publications

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“…Our results also showed that in the umbilical cord tissue homogenates, the activation of MAPK pathway is higher in neonates with BPD compared to healthy controls. These findings corroborate a previous study showing that the early versus late transplantation of erythropoietin gene‐modified stem cells (EPO mesenchymal stem cells) might mitigate BPD injury by inhibiting the inflammatory response through the downregulation of p38/MAPK pathway 22 . Our study also suggests that there is a possible link between BPD and HTLV‐1 infection.…”

Section: Discussionsupporting

confidence: 92%

Weighted gene coexpression network reveals downregulation of genes in bronchopulmonary dysplasia

Liu

et al. 2020

Pediatric Pulmonology

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Background: Bronchopulmonary dysplasia (BPD) is a serious lung disease observed in premature infants, known to cause considerable morbidity and mortality. Its prognosis is influenced by a complex network of genetic interactions. In this study, we determined the potential key factors in the pathogenesis of this condition. Methods: We constructed scale-free gene coexpression network using weighted gene coexpression network analysis. The analysis was carried out on the GSE8586 dataset, which contains the expression profiles of umbilical cord tissue homogenates from 20 neonates with BPD and 34 unaffected controls. Results: Our analysis identified one significantly downregulated coexpression module related to the BPD phenotype. It was significantly enriched in genes related to human T-cell leukemia virus infection and the mitogen-activated protein kinase pathway. In this module, the expression of the following four hub genes in infants with BPD was significantly decreased: Fos proto-oncogene (FOS), BTG antiproliferation factor 2 (BTG2), Jun proto-oncogene (JUN), and early growth response protein 1 (EGR1). The downregulation of these hub genes was verified in clinical samples derived from blood and umbilical cord tissue.

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Section: Discussionsupporting

confidence: 92%

Weighted gene coexpression network reveals downregulation of genes in bronchopulmonary dysplasia

Liu

et al. 2020

Pediatric Pulmonology

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“…These findings indicated that two peptides may play an antiinflammatory role in the process of BPD. And previous studies have shown that the regulation of inflammation-related signal pathways such as p38 mitogen activated protein kinases (p38MAPK) signal pathways and nuclear factor-κB (NF-κB) signal pathway can reduce the level of pro-inflammatory cytokines, thus relieving the pulmonary inflammation of BPD [ 76 , 77 ]. Combined with previous studies, we consider that the two peptides secreted from hUC-MSCs may decrease the production of pro-inflammatory cytokines through inflammation-related signal pathways and further researches need to be conducted to validate the possible pathway.…”

Section: Discussionmentioning

confidence: 99%

Peptidome analysis of umbilical cord mesenchymal stem cell (hUC-MSC) conditioned medium from preterm and term infants

Wang

Zhang

et al. 2020

Stem Cell Res Ther

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Background The therapeutic role of mesenchymal stem cells (MSCs) has been widely confirmed in several animal models of premature infant diseases. Micromolecule peptides have shown promise for the treatment of premature infant diseases. However, the potential role of peptides secreted from MSCs has not been studied. The purpose of this study is to help to broaden the knowledge of the hUC-MSC secretome at the peptide level through peptidomic profile analysis. Methods We used tandem mass tag (TMT) labeling technology followed by tandem mass spectrometry to compare the peptidomic profile of preterm and term umbilical cord MSC (hUC-MSC) conditioned medium (CM). Gene Ontology (GO) enrichment analysis and ingenuity pathway analysis (IPA) were conducted to explore the differentially expressed peptides by predicting the functions of their precursor proteins. To evaluate the effect of candidate peptides on human lung epithelial cells stimulated by hydrogen peroxide (H2O2), quantitative real-time PCR (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were, respectively, adopted to detect inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression levels at the mRNA and protein levels. Results A total of 131 peptides derived from 106 precursor proteins were differentially expressed in the preterm hUC-MSC CM compared with the term group, comprising 37 upregulated peptides and 94 downregulated peptides. Bioinformatics analysis showed that these differentially expressed peptides may be associated with developmental disorders, inflammatory response, and organismal injury. We also found that peptides 7118TGAKIKLVGT7127 derived from MUC19 and 508AAAAGPANVH517 derived from SIX5 reduced the expression levels of TNF-α, IL-1β, and IL-6 in H2O2-treated human lung epithelial cells. Conclusions In summary, this study provides further secretomics information on hUC-MSCs and provides a series of peptides that might have antiinflammatory effects on pulmonary epithelial cells and contribute to the prevention and treatment of respiratory diseases in premature infants.

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“…These ndings indicated that two peptides may play an anti-in ammatory role in the process of BPD. And previous studies have shown that the regulation of in ammation-related signal pathways such as p38 mitogen activated protein kinases (p38MAPK) signal pathways and nuclear factor-κB (NF-κB) signal pathway can reduce the level of pro-in ammatory cytokines, thus relieving the pulmonary in ammation of BPD [78,79].…”

Section: Discussionmentioning

confidence: 99%

Peptidome Analysis of Umbilical Cord Mesenchymal Stem Cell (hUC-MSC) Conditioned Medium from Preterm and Term Infants

Wang

Zhang

et al. 2020

Preprint

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Background: The therapeutic role of mesenchymal stem cells (MSCs) has been widely confirmed in several animal models of premature infant diseases. Micromolecule peptides have shown promise for the treatment of premature infant diseases. However, the potential role of peptides secreted from MSCs has not been studied. The purpose of this study is to helps to broaden the knowledge of the hUC-MSC secretome at the peptide level through peptidomic profile analysis.Methods: We used tandem mass tag (TMT) labeling technology followed by tandem mass spectrometry to compare the peptidomic profile of preterm and term umbilical cord MSC (hUC-MSC) conditioned medium (CM). Gene Ontology (GO) enrichment analysis and Ingenuity Pathway Analysis (IPA) were conducted to explore the differentially expressed peptides by predicting the functions of their precursor proteins. To evaluate the effect of candidate peptides on human lung epithelial cells stimulated by hydrogen peroxide (H2O2), quantitative real-time PCR (qRT-PCR), western blot analysis and enzyme-linked immunosorbent assay (ELISA) were respectively adopted to detect inflammatory cytokines (TNF-α, IL-1β and IL-6) expression levels at the mRNA and protein levels,Results: A total of 131 peptides derived from 106 precursor proteins were differentially expressed in the preterm hUC-MSC CM compared with the term group, comprising 37 up-regulated peptides and 94 down-regulated peptides. Bioinformatics analysis showed that these differentially expressed peptides may be associated with developmental disorders, inflammatory response and organismal injury. We also found that peptides 7118TGAKIKLVGT7127 derived from MUC19 and 508AAAAGPANVH517 derived from SIX5 reduced the expression levels of TNF-α, IL-1β and IL-6 in H2O2-treated human lung epithelial cells.Conclusions: In summary, this study provides further secretomics information on hUC-MSCs and provides a series of peptides that might have antiinflammatory effects on pulmonary epithelial cells and contribute to the prevention and treatment of respiratory diseases in premature infants.

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Timing of erythropoietin modified mesenchymal stromal cell transplantation for the treatment of experimental bronchopulmonary dysplasia

Cited by 12 publications

References 14 publications

Weighted gene coexpression network reveals downregulation of genes in bronchopulmonary dysplasia

Weighted gene coexpression network reveals downregulation of genes in bronchopulmonary dysplasia

Peptidome analysis of umbilical cord mesenchymal stem cell (hUC-MSC) conditioned medium from preterm and term infants

Peptidome Analysis of Umbilical Cord Mesenchymal Stem Cell (hUC-MSC) Conditioned Medium from Preterm and Term Infants

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