期刊
RESPIRATORY RESEARCH
卷 14, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/1465-9921-14-37
关键词
Alveolar type II cell; Bronchopulmonary dysplasia; Dexamethasone; Stem cell; Regeneration
资金
- National Center for Research Resources [5 P20 RR018728-10]
- National Institute of General Medical Sciences from the National Institutes of Health [8 P20 GM103537-10]
- Perkin-Elmer/Viacord
Background: We investigated the capacity of expanded cord blood-derived CD34+ hematopoietic progenitor cells to undergo respiratory epithelial differentiation ex vivo, and to engraft and attenuate alveolar disruption in injured newborn murine lungs in vivo. Methods: Respiratory epithelial differentiation was studied in CD34+ cells expanded in the presence of growth factors and cytokines (basic medium), in one group supplemented with dexamethasone (DEX). Expanded or freshly isolated CD34+ cells were inoculated intranasally in newborn mice with apoptosis-induced lung injury. Pulmonary engraftment, lung growth and alveolarization were studied at 8 weeks post-inoculation. Results: SP-C mRNA expression was seen in 2/7 CD34+ cell isolates expanded in basic media and in 6/7 isolates expanded in DEX, associated with cytoplasmic SP-C immunoreactivity and ultrastructural features suggestive of type II cell-like differentiation. Administration of expanding CD34+ cells was associated with increased lung growth and, in animals treated with DEX-exposed cells, enhanced alveolar septation. Freshly isolated CD34+ cells had no effect of lung growth or remodeling. Lungs of animals treated with expanded CD34+ cells contained intraalveolar aggregates of replicating alu-FISH-positive mononuclear cells, whereas epithelial engraftment was extremely rare. Conclusion: Expanded cord blood CD34+ cells can induce lung growth and alveolarization in injured newborn lungs. These growth-promoting effects may be linked to paracrine or immunomodulatory effects of persistent cord blood-derived mononuclear cells, as expanded cells showed limited respiratory epithelial transdifferentiation.
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