Akram, KM and Samad, S and Spiteri, MA and Forsyth, NR (2013) Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms. Respiratory Research, 14. 9 - ?. ISSN 1465-993X

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Abstract

BACKGROUND: Mesenchymal stem cells (MSC) are in clinical trials for widespread indications including musculoskeletal, neurological, cardiac and haematological disorders. Furthermore, MSC can ameliorate pulmonary fibrosis in animal models although mechanisms of action remain unclear. One emerging concept is that MSCs may have paracrine, rather than a functional, roles in lung injury repair and regeneration. METHODS: To investigate the paracrine role of human MSC (hMSC) on pulmonary epithelial repair, hMSC-conditioned media (CM) and a selected cohort of hMSC-secretory proteins (identified by LC-MS/MS mass spectrometry) were tested on human type II alveolar epithelial cell line A549 cells (AEC) and primary human small airway epithelial cells (SAEC) using an in vitro scratch wound repair model. A 3D direct-contact wound repair model was further developed to assess the migratory properties of hMSC. RESULTS: We demonstrate that MSC-CM facilitates AEC and SAEC wound repair in serum-dependent and -independent manners respectively via stimulation of cell migration. We also show that the hMSC secretome contains an array of proteins including Fibronectin, Lumican, Periostin, and IGFBP-7; each capable of influencing AEC and SAEC migration and wound repair stimulation. In addition, hMSC also show a strong migratory response to AEC injury as, supported by the observation of rapid and effective AEC wound gap closure by hMSC in the 3D model. CONCLUSION: These findings support the notion for clinical application of hMSCs and/or their secretory factors as a pharmacoregenerative modality for the treatment of idiopathic pulmonary fibrosis (IPF) and other fibrotic lung disorders.

Item Type: Article
Uncontrolled Keywords: Mesenchymal stem cells; idiopathic pulmonary fibrosis; Alveolar epithelial wound repair; MSC secretory proteins
Subjects: ?? Cell Line ??
?? Cell Movement ??
?? Humans ??
?? Mesenchymal Stromal Cells ??
?? Paracrine Communication ??
?? Pulmonary Alveoli ??
R Medicine > R Medicine (General)
?? Respiratory Mucosa ??
?? Wound Healing ??
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Related URLs:
Depositing User: Symplectic
Date Deposited: 14 Dec 2016 08:48
Last Modified: 14 Dec 2016 08:48
URI: http://eprints.keele.ac.uk/id/eprint/2633

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