Editors' ChoiceLUNG INJURY

From One Stem Cell to Another

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Science Translational Medicine  27 Jun 2012:
Vol. 4, Issue 140, pp. 140ec114
DOI: 10.1126/scitranslmed.3004509

As a result of strong preclinical data, mesenchymal stem cells (MSCs) have been proposed as a potential therapy for a wide variety of lung diseases, ranging from chronic obstructive pulmonary disease to acute lung injury to bronchopulmonary dysplasia, the most common type of chronic lung disease due to premature birth. In these settings, the benefits of MSCs have been largely attributed to anti-inflammatory factors secreted by these cells, although some recent data have suggested that MSCs may also enhance repair after lung injury. Tropea and colleagues set out to test the hypothesis that MSCs contribute to lung repair by activating endogenous lung stem cells, specifically bronchioalveolar stem cells (BASCs).

Previous work by the same research group suggested that a subset of Clara cells (secretory cells in the distal airways with diverse protective functions), which the scientists termed BASCs, proliferate in response to lung injury and may give rise to both bronchiolar and alveolar epithelial cells (although this finding has been contested by other investigators). In the current study, the authors used a mouse model of neonatal hyperoxic lung injury designed to mimic bronchopulmonary dysplasia and first confirmed that intravenous MSCs or their conditioned media prevented the pathologic loss of alveolar surface area characteristic of bronchopulmonary dysplasia, as others had previously shown. Next, they found that MSCs or their conditioned media led to a significant increase in the number of BASCs identified by using immunofluorescence microscopy as compared with control treatments. In a cell culture model, treatment of BASCs with MSC-conditioned media increased the colony-forming ability of the BASCs, further demonstrating that the mechanism of benefit is cell contact-independent. Of note, these effects did not seem to be due to growth factors such as keratinocyte growth factor, which mediate some of the beneficial effects of MSCs in acute lung injury models. Last, lineage-tracing experiments suggested that BASCs contribute to reestablishing the lung epithelium after injury, although these findings were not definitive and were obtained from a different mouse model (in which lungs were injured with bleomycin). Although far from conclusive, this work by Tropea and colleagues provides further evidence that MSCs may contribute to lung repair after injury via stimulation of endogenous lung stem cell populations.

K. A. Tropea et al., Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia. Am. J. Physiol. Lung Cell. Mol. Physiol. 302, L829–L837 (2012). [Abstract]

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