Ex vivo expanded human cord blood-derived hematopoietic progenitor cells induce lung growth and alveolarization in injured newborn lungs |
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Authors: | Quanfu Mao Sharon Chu Sailaja Ghanta James F Padbury Monique E De Paepe |
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Institution: | 1.Department of Pathology, Women and Infants Hospital, Providence, RI, USA;2.Department of Pediatrics, Providence, RI, USA;3.Department of Pathology and Laboratory Medicine, 101 Dudley Street, Providence, RI, 02905, USA;4.Department of Pediatrics, Alpert Medical School of Brown University, Providence, RI, 02905, USA |
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Abstract: | BackgroundWe 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.MethodsRespiratory 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.ResultsSP-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.ConclusionExpanded 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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Keywords: | Alveolar type II cell Bronchopulmonary dysplasia Dexamethasone Stem cell Regeneration |
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