Human amnion epithelial cell transplantation abrogates lung fibrosis and augments repair.
BACKGROUND
Chronic lung disease characterized by loss of lung tissue, inflammation, and fibrosis represents a major global health burden. Cellular therapies that could restore pneumocytes and reduce inflammation and fibrosis would be a major advance in management.


OBJECTIVE
To determine whether human amnion epithelial cells (hAECs), isolated from term placenta and having stem cell-like and antiinflammatory 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 to determine whether the cells could adopt an alveolar epithelial phenotype. Undifferentiated primary hAECs were also injected parenterally into SCID mice after bleomycin-induced lung injury and analyzed for production of surfactant protein (SP)-A, SP-B, SP-C, and SP-D. Mouse lungs were also analyzed for inflammation and collagen deposition.


RESULTS
hAECs grown in small airway growth medium 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 2 weeks post-transplantation produced SPs. hAECs remained engrafted over the 4-week test period. hAEC administration reduced inflammation in association with decreased monocyte chemoattractant protein-1, tumor necrosis factor-alpha, IL-1 and -6, and profibrotic transforming growth factor-beta 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 the tissue inhibitors of matrix metalloproteinase-1 and 2.


CONCLUSIONS
hAECs offer promise as a cellular therapy for alveolar restitution and to reduce lung inflammation and fibrosis.
Moodley
Yuben
Y
F.R.A.C.P. School of Medicine and Pharmacology, University of Western Australia, 50 Murray Street, Perth, Western Australia 6000, Australia. yuben.moodley@uwa.edu.au
Ilancheran
Sivagami
S
Samuel
Chrishan
C
Vaghjiani
Vijesh
V
Atienza
Daniel
D
Williams
Elizabeth D
ED
Jenkin
Graham
G
Wallace
Euan
E
Trounson
Alan
A
Manuelpillai
Ursula
U
D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000187:drug effects; D000650:Amnion / Q000166:cytology* / Q000637:transplantation*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001761:Bleomycin; D002454:Cell Differentiation / Q000187:drug effects; D017690:Cell Transplantation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004587:Electrophoresis, Agar Gel; D004847:Epithelial Cells / Q000637:transplantation*; D005260:Female; D006801:Humans; D055370:Lung Injury / Q000139:chemically induced / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D010920:Placenta / Q000166:cytology; D011014:Pneumonia / Q000473:pathology / Q000628:therapy; D011247:Pregnancy; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation
D000893:Anti-Inflammatory Agents; D001761:Bleomycin