Ex vivo expanded human cord blood-derived hematopoietic progenitor cells induce lung growth and alveolarization in injured newborn lungs

Respiratory Research

Monique E De Paepe³  James F Padbury⁴  Sailaja Ghanta¹  Sharon Chu²  Quanfu Mao³ 

[1] Department of Pediatrics, Providence, RI, USA;Department of Pathology, Women and Infants Hospital, Providence, RI, USA;Department of Pathology and Laboratory Medicine, 101 Dudley Street, Providence, RI, 02905, USA;Department of Pediatrics, Alpert Medical School of Brown University, Providence, RI, 02905, USA

关键词: Regeneration;    Stem cell;    Dexamethasone;    Bronchopulmonary dysplasia;    Alveolar type II cell;   

Others  :  794851
DOI  :  10.1186/1465-9921-14-37

 received in 2012-12-17, accepted in 2013-03-19,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Mao et al.; licensee BioMed Central Ltd.

【 图 表 】

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