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Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice

Monz, Dominik ; Tutdibi, Erol ; Mildau, Céline ; Shen, Jie ; Kasoha, Mariz ; Laschke, Matthias W ; Roolfs, Torge ; Schmiedl, Andreas ; Tschernig, Thomas ; Bieback, Karen ; Gortner, Ludwig Bellusci, Saverio

PloS one, 2013-09, Vol.8 (9), p.e74740-e74740 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice
Autor: Monz, Dominik ; Tutdibi, Erol ; Mildau, Céline ; Shen, Jie ; Kasoha, Mariz ; Laschke, Matthias W ; Roolfs, Torge ; Schmiedl, Andreas ; Tschernig, Thomas ; Bieback, Karen ; Gortner, Ludwig
Bellusci, Saverio
Assuntos: Allografts ; Alveolar Epithelial Cells - pathology ; Alveolar Epithelial Cells - ultrastructure ; Analysis ; Animals ; Animals, Newborn ; Blood ; Bronchopulmonary Dysplasia - genetics ; Bronchopulmonary Dysplasia - metabolism ; Bronchopulmonary Dysplasia - pathology ; Bronchopulmonary Dysplasia - therapy ; Cord blood ; Cord Blood Stem Cell Transplantation ; Cruelty to animals ; Cytokines - metabolism ; Disease ; Disease Models, Animal ; Dysplasia ; Electron microscopy ; Fetal Blood - cytology ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation ; Histomorphometry ; Humans ; Hyperoxia ; Hypoxia ; IL-1β ; Infants (Premature) ; Inflammation ; Insulin-like growth factor I ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - metabolism ; Leukocytes, Mononuclear - transplantation ; Lung - metabolism ; Lung - pathology ; Lungs ; Mice ; Molecular structure ; Neonates ; Newborn babies ; Offspring ; Pediatrics ; Premature birth ; Premature infants ; Proteins ; RNA ; Rodents ; Septum ; Stem cell transplantation ; Stem cells ; Thickness ; TOR protein ; Umbilical cord
É parte de: PloS one, 2013-09, Vol.8 (9), p.e74740-e74740
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: DM ET LG. Wrote the manuscript: DM ET LG. Supported conception and design of the animal experiments: MWL TT. Performed work with the animals: DM ET CM JS. Performed the cell isolation: DM CM JS MK KB. Performed the qPCR experiments: DM CM JS MK. Performed the bead assay experiments: DM MK. Performed the stereological experiments: TR AS. Analyzed the animal data: DM ET CM LG. Analyzed the qPCR experiments: DM ET CM JS MK. Analyzed the bead assay data: DM MK. Analyzed the stereological data: TR AS. Contributed reagents, material and analysis tools for the animal, qPCR and bead assay experiments: LG. Contributed reagents and material for the animal experiments and cell isolation: MWL. Contributed material and reagents for the stereological experiments: AS. Wrote the stereology sections in Materials and Methods and the Results: AS.
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice

Monz, Dominik ; Tutdibi, Erol ; Mildau, Céline ; Shen, Jie ; Kasoha, Mariz ; Laschke, Matthias W ; Roolfs, Torge ; Schmiedl, Andreas ; Tschernig, Thomas ; Bieback, Karen ; Gortner, Ludwig Bellusci, Saverio

United States: Public Library of Science

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