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

• Published in: Respiratory research 2013-03, Vol.14 (1), p.37-37, Article 37
• Main Authors: Mao, Quanfu, Chu, Sharon, Ghanta, Sailaja, Padbury, James F, De Paepe, Monique E
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Apoptosis; Care and treatment; Cell differentiation; Complications and side effects; Cord Blood Stem Cell Transplantation - methods; Cytokines; Dexamethasone; Fetal blood; Growth; Health aspects; Hematopoietic Stem Cell Transplantation - methods; Infants (Newborn); Infants (Premature); Injuries; Lung - growth & development; Lung - surgery; Lung diseases; Lung Injury - physiopathology; Lung Injury - surgery; Lungs; Mice; Mice, Transgenic; Premature birth; Pulmonary Alveoli - growth & development; Risk factors; RNA; Rodents; Stem cells; Studies; Transplants & implants; Treatment Outcome
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/1465-9921-14-37

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. 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. 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. 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.