Cell-based tissue engineering for lung regeneration

Abstract

Emphysema is a chronic lung disease characterized by alveolar enlargement and tissue loss. Tissue engineering represents an attractive potential for regeneration of several organ systems. The complex three-dimensional architectural structure of lung parenchyma requiring connections of alveolar units to airways and the pulmonary circulation makes this strategy less optimistic. In the present study, we used Gelfoam sponge as a scaffold material, supplemented with fetal rat lung cells as progenitors, to explore the potential application of cell-based tissue engineering for lung regeneration in adult rats. After injection into lung parenchyma, the sponge showed porous structures similar to alveolar units. It did not induce severe local inflammatory response. Fetal lung cells in the sponge were able to survive in the adult lung for at least 35 days, determined by CMTMR [5-(and-6)-{[(4-chloromethyl)benzoyl]amino}tetramethylrhodamine] labeling. Proliferation of cells within the sponge was demonstrated in vivo by bromodeoxyuridine (BrdU) labeling. Cells formed “alveolar-like structures” at the border between the sponge and the surrounding lung tissue with positive immunohistochemical staining for epithelial and endothelial cells. Neovascularization of the sponge was demonstrated with India ink perfusion. The sponge degraded after several months. This study suggests that cell-based tissue engineering possesses the potential to regenerate alveolar-like structures, an important step towards our ultimate goal of lung regeneration.

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

“…This suggests that culture of stem cells in an artificial scaffolding in medium conducive to lung epithleial development may be a robust means of lung regeneration than achieved with routine tissue culturing [29][30][31][32][33].…”

Novel Methods for Delivery of Cell-Based Therapies

“…The authors described the delivery of fewer amounts of unlabeled dendritic cells intratracheally resulting in increased local leukocyte infiltration, decreased tumor progression and increased survival due to dendritic cells' effects within the cancerous lung tissue. Andrade et al (15), in work most closely related to ours, delivered rat FPC into the pulmonary cavity as a potential method for the treatment of emphysema. They demonstrated adequate delivery of cells directly into the lung parenchyma, without any local inflammatory reaction.…”

“…Different types of cells have been delivered intratracheally or intrapulmonary (13)(14)(15) with no clear consensus regarding adequacy of delivery that would translate into potential successful therapeutic results. The intratracheal administration of mesenchymal stem cells as a means of treating endothelial dysfunction in pulmonary hypertension was described by Baber et al (13).…”

Stem cell therapy for idiopathic pulmonary fibrosis: How far are we from the bench to the bedside?

“…The xenograft functioned sufficiently as the conducting airway without any need for intake of immunosuppressants. There are also observations that fetal lung cells imbedded in matrigel sponges are able to form the branching airway structures [83,84]. However, as compared with the trachea, the lung is a far more delicate system that consists of 16 grades of bronchi, numerous blood vessels and capillaries and more than 40 cell types.…”