Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice.
Bronchopulmonary dysplasia (BPD) presents a major threat of very preterm birth and treatment options are still limited. Stem cells from different sources have been used successfully in experimental BPD, induced by postnatal hyperoxia.We investigated the effect of umbilical cord blood mononuclear cel...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3778007?pdf=render |
| _version_ | 1818120224239517696 |
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| author | Dominik Monz Erol Tutdibi Céline Mildau Jie Shen Mariz Kasoha Matthias W Laschke Torge Roolfs Andreas Schmiedl Thomas Tschernig Karen Bieback Ludwig Gortner |
| author_facet | Dominik Monz Erol Tutdibi Céline Mildau Jie Shen Mariz Kasoha Matthias W Laschke Torge Roolfs Andreas Schmiedl Thomas Tschernig Karen Bieback Ludwig Gortner |
| author_sort | Dominik Monz |
| collection | DOAJ |
| description | Bronchopulmonary dysplasia (BPD) presents a major threat of very preterm birth and treatment options are still limited. Stem cells from different sources have been used successfully in experimental BPD, induced by postnatal hyperoxia.We investigated the effect of umbilical cord blood mononuclear cells (MNCs) in a new double-hit mouse model of BPD.For the double-hit, date mated mice were subjected to hypoxia and thereafter the offspring was exposed to hyperoxia. Human umbilical cord blood MNCs were given intraperitoneally by day P7. As outcome variables were defined: physical development (auxology), lung structure (histomorphometry), expression of markers for lung maturation and inflammation on mRNA and protein level. Pre- and postnatal normoxic pups and sham treated double-hit pups served as control groups.Compared to normoxic controls, sham treated double-hit animals showed impaired physical and lung development with reduced alveolarization and increased thickness of septa. Electron microscopy revealed reduced volume density of lamellar bodies. Pulmonary expression of mRNA for surfactant proteins B and C, Mtor and Crabp1 was reduced. Expression of Igf1 was increased. Treatment with umbilical cord blood MNCs normalized thickness of septa and mRNA expression of Mtor to levels of normoxic controls. Tgfb3 mRNA expression and pro-inflammatory IL-1β protein concentration were decreased.The results of our study demonstrate the therapeutic potential of umbilical cord blood MNCs in a new double-hit model of BPD in newborn mice. We found improved lung structure and effects on molecular level. Further studies are needed to address the role of systemic administration of MNCs in experimental BPD. |
| first_indexed | 2024-12-11T05:22:41Z |
| format | Article |
| id | doaj.art-c1fb7ee2e59e45f080f01e3d13b15540 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T05:22:41Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c1fb7ee2e59e45f080f01e3d13b155402022-12-22T01:19:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7474010.1371/journal.pone.0074740Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice.Dominik MonzErol TutdibiCéline MildauJie ShenMariz KasohaMatthias W LaschkeTorge RoolfsAndreas SchmiedlThomas TschernigKaren BiebackLudwig GortnerBronchopulmonary dysplasia (BPD) presents a major threat of very preterm birth and treatment options are still limited. Stem cells from different sources have been used successfully in experimental BPD, induced by postnatal hyperoxia.We investigated the effect of umbilical cord blood mononuclear cells (MNCs) in a new double-hit mouse model of BPD.For the double-hit, date mated mice were subjected to hypoxia and thereafter the offspring was exposed to hyperoxia. Human umbilical cord blood MNCs were given intraperitoneally by day P7. As outcome variables were defined: physical development (auxology), lung structure (histomorphometry), expression of markers for lung maturation and inflammation on mRNA and protein level. Pre- and postnatal normoxic pups and sham treated double-hit pups served as control groups.Compared to normoxic controls, sham treated double-hit animals showed impaired physical and lung development with reduced alveolarization and increased thickness of septa. Electron microscopy revealed reduced volume density of lamellar bodies. Pulmonary expression of mRNA for surfactant proteins B and C, Mtor and Crabp1 was reduced. Expression of Igf1 was increased. Treatment with umbilical cord blood MNCs normalized thickness of septa and mRNA expression of Mtor to levels of normoxic controls. Tgfb3 mRNA expression and pro-inflammatory IL-1β protein concentration were decreased.The results of our study demonstrate the therapeutic potential of umbilical cord blood MNCs in a new double-hit model of BPD in newborn mice. We found improved lung structure and effects on molecular level. Further studies are needed to address the role of systemic administration of MNCs in experimental BPD.http://europepmc.org/articles/PMC3778007?pdf=render |
| spellingShingle | Dominik Monz Erol Tutdibi Céline Mildau Jie Shen Mariz Kasoha Matthias W Laschke Torge Roolfs Andreas Schmiedl Thomas Tschernig Karen Bieback Ludwig Gortner Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice. PLoS ONE |
| title | Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice. |
| title_full | Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice. |
| title_fullStr | Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice. |
| title_full_unstemmed | Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice. |
| title_short | Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice. |
| title_sort | human umbilical cord blood mononuclear cells in a double hit model of bronchopulmonary dysplasia in neonatal mice |
| url | http://europepmc.org/articles/PMC3778007?pdf=render |
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