Overexpression of Sonic Hedgehog in the Lung Mimics the Effect of Lung Injury and Compensatory Lung Growth on Pulmonary Sca-1 and CD34 Positive Cells

Abstract

Cells localized in the bronchioalveolar duct junction of the murine lung have been identified as potential bronchioalveolar stem cells. Based on the surface marker expression, two main phenotypes have been proposed: Sca-1(+), CD34(+), CD45(-), Pecam(-) and Sca-1(low), CD34(-) CD45(-), Pecam(-) cells. An increase in the number of Sca-1(+), CD34(+) CD45(-), Pecam(-) cells and activation of the sonic hedgehog (Shh) pathway was observed following unilateral pneumonectomy and naphthalene-induced airway injury. Overexpression of Shh in the respiratory tract also resulted in an increase of this cell population. Syngeneic transplantation of beta-galactosidase-expressing bone marrow cells demonstrated that the increase of Sca-1(+), CD34(+), CD45(-), Pecam(-) cells in the lung was a result of local proliferation. Intratracheal administration of purified Shh-stimulated Sca-1(+), CD45(-), Pecam(-) cells coexpressing CD34 to syngeneic mice following pneumonectomy resulted in engraftment of these cells predominantly in the airways for up to 3 months, whereas Sca-1(-), CD45(-), Pecam(-) cells did not engraft. This study suggests that local Sca-1(+), CD34(+), CD45(-), Pecam(-) cells are stimulated during compensatory lung growth, following airway injury and overexpression of Shh and have some potential to engraft in the airways, without showing clonal properties in vivo.