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Engraftment of Neonatal Lung Fibroblasts into the Normal and Elastase-Injured Lung

Pulmonary Center, Boston University School of Medicine, and the VA Boston Healthcare System, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Ronald H. Goldstein, M.D., The Pulmonary Center, Boston University School of Medicine, 715 Albany Street, R-304 Boston, MA 02118. E-mail: rgoldstein{at}lung.bumc.bu.edu

Interstitial fibroblasts are an integral component of the alveolar wall. These cells produce matrix proteins that maintain the extracellular scaffold of alveolar structures. Emphysema is characterized by airspace enlargement resulting from the loss of alveolar cellularity and matrix. In this study, we explored the endotracheal delivery of fibroblasts to the lung parenchyma as a means of repairing damaged alveolar structures directly or indirectly for the delivery of transgenes. Fibroblasts were isolated from the lungs of neonatal transgenic mice expressing GFP during the period of rapid alveolarization. These GFP⁺ cells maintained their myofibroblast phenotype in culture and expressed elastin and -smooth muscle actin mRNA. We administered GFP⁺ fibroblasts to saline- and elastase-treated mice by endotracheal instillation. We detected more GFP⁺ fibroblasts in the alveolar walls and in the interstitial areas of elastase-injured lungs than in normal lungs as assessed by immunohistochemistry and fluorescent imaging. The presence of GFP⁺ fibroblasts in the interstitium demonstrated transepithelial migration of these cells. Expression of GFP⁺ fibroblasts in recipient lungs was maintained for at least 20 d after endotracheal administration. These cells synthesize matrix components including elastin in vitro and could contribute to restoring the structural integrity of the alveolar wall.

Key Words: elastase • elastin • emphysema • fibroblasts