Acute Lung Injury with Endotoxin or NO2 Does Not Enhance Development of Airway Epithelium from Bone Marrow

Abstract

Adult marrow-derived stem cells can localize to lung and acquire immunophenotypic characteristics of lung epithelial cells. Lung injury increases recruitment of the marrow-derived cells. We speculated that comparing patterns of lung engraftment following different lung injuries would provide insight into potential mechanisms by which marrow-derived cells were recruited to lung. To evaluate this, adult female C57Bl/6 mice irradiated and engrafted with marrow from adult male transgenic GFP mice were exposed to either intranasal inhalation of endotoxin (25 microg/mouse) or 3 days of 25 ppm NO(2) and then compared 1 or 3 months later to transplanted but otherwise uninjured mice. In all cases, the majority of marrow-derived cells recruited to lung were CD45(+) leukocytes. In lungs of transplanted but otherwise uninjured mice, small numbers of CD45(-) donor-derived cells in alveolar septae stained positively for pro-surfactant protein C. Rare donor-derived cells located in the airway epithelium stained positively with cytokeratin. Subsequent exposure of engrafted mice to NO(2) or endotoxin did not significantly increase the number or pattern of donor-derived CD45(-) cells found in recipient lungs. These results suggest that NO(2) or endotoxin lung injury does not result in significant engraftment of marrow-derived cells in lung.

Derivation of Lung Epithelium from Human Cord Blood–derived Mesenchymal Stem Cells

“…The apparent rate of engraftment of CB-MSCs is similar to the low levels of engraftment we and others have observed with systemically administered adult mouse marrow-derived MSCs (2,5,9,42). There are, however, a number of variables that might have affected engraftment in these studies.…”

Stem cells and cell therapies for cystic fibrosis and other lung diseases

“…This has been described in models of lung inflammation, emphysema, and fibrosis and has been observed with several cell populations including MSCs [41][42][43][44][45]. Notably, systemic administration of MSCs immediately after intratracheal bleomycin administration decreased subsequent lung fibrosis and collagen accumulation [43].…”

Lung Stem Cell Update: Promise and Controversy

“…The results from both studies suggest that artifactual co-localization of markers, in the face of a flood of phagocytic hematopoietic cell types, many dead cells, and abundant autofluoresence in lung tissue, is more likely than actual transdifferentiation. Another recent study in mice reports absence of significant parenchymal engraftment of marrow-derived cells after endotoxin or NO 2 lung injury [21].…”