Human amnion epithelial cell transplantation abrogates lung fibrosis and augments repair

Moodley, Yuben, Ilancheran, Sivagami, Samuel, Chrishan, Vaghjiani, Vijesh, Atienza, Daniel, Williams, Elizabeth D., Jenkin, Graham, Wallace, Euan, Trounson, Alan, & Manuelpillai, Ursula (2010) Human amnion epithelial cell transplantation abrogates lung fibrosis and augments repair. American Journal of Respiratory and Critical Care Medicine, 182(5), pp. 643-651.

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Abstract

Rationale: 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.

Objectives: 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.

Measurements and Main 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 posttransplantation 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-a, IL-1 and -6, and profibrotic transforming growth factor-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 the tissue inhibitors f matrix metalloproteinase-1 and 2.

Conclusions: hAECs offer promise as a cellular therapy for alveolar restitution and to reduce lung inflammation and fibrosis.

Impact and interest:

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ID Code: 77748
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Keywords: Cellular therapies, lung disease, stem cells, human amnion epithelial cell transplantation, lung fibrosis, tissue repair, fetal membranes, bleomycin, amnion epithelial cells
DOI: 10.1164/rccm.201001-0014OC
ISSN: 1535-4970
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > OTHER MEDICAL AND HEALTH SCIENCES (119900) > Medical and Health Sciences not elsewhere classified (119999)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 The American Thoracic Society
Deposited On: 16 Oct 2014 06:27
Last Modified: 22 Jan 2015 02:16

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