Authors:
Yuben Moodley, Sivagami Ilancheran, Chrishan Samuel, Vijesh Vaghjiani, Daniel Atienza, Elizabeth D Williams, Graham Jenkin, Euan Wallace, Alan Trounson, and Ursula Manuelpillai
Summary:
Rationale - Chronic lung disease characterized by loss of lung tissue, inflammation and fibrosis represent a major global health burden. Cellular therapies that could restore pneumocytes, reduce inflammation and fibrosis would be a major advance in management.
Objectives - To determine if human amnion epithelial cells (hAECs), isolated from term placenta and have stem cell-like and anti-inflammatory properties, could adopt an alveolar epithelial phenotype and repair a murine model of Bleomycin-induced lung injury.
Methods - Primary hAECs were cultured in Small Airway Growth Medium (SAGM) to determine if the cells could adopt an alveolar epithelial phenotype. Undifferentiated primary hAECs were also injected parenterally into SCID mice following Bleomycin-induced lung injury and analyzed for production of surfactant protein (SP)-A, -B, -C and -D. Mouse lungs were also analyzed for inflammation and collagen deposition.
Measurements & Main Results - hAECs grown in SAGM developed an alveolar epithelial phenotype with lamellar body formation, production of SPs A-D and SP-D secretion. Although hAECs injected into mice lacked SPs, hAECs recovered from mouse lungs two weeks post-transplantation produced SPs. hAECs remained engrafted over the four week test period. hAEC administration reduced inflammation in association with decreased MCP-1, TNF-a, IL-1 and IL-6 and pro-fibrotic TGF-b in mouse lungs. In addition, lung collagen content was significantly reduced by hAEC treatment as a possible consequence of increased degradation by matrix metalloproteinase-2 and down-regulation of their inhibitors the tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2.
Conclusion - hAECs offer promise as a cellular therapy for alveolar restitution and reducing lung inflammation and fibrosis.
Source:
American Journal of Respiratory & Critical Care Medicine; (06/03/10)