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


OBJECTIVE
We investigated the effect of umbilical cord blood mononuclear cells (MNCs) in a new double-hit mouse model of BPD.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pediatrics and Neonatology, Saarland University, Homburg, Saar, Germany.
Dominik
D
Monz
Erol
E
Tutdibi
Céline
C
Mildau
Jie
J
Shen
Mariz
M
Kasoha
Matthias W
MW
Laschke
Torge
T
Roolfs
Andreas
A
Schmiedl
Thomas
T
Tschernig
Karen
K
Bieback
Ludwig
L
Gortner
D056809:Alveolar Epithelial Cells / Q000473:pathology / Q000648:ultrastructure; D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D036101:Cord Blood Stem Cell Transplantation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D018496:Hyperoxia; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000637:transplantation*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice
D016207:Cytokines