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Open Access Highly Accessed Research

Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms

Khondoker M Akram1, Sohel Samad1, Monica A Spiteri12 and Nicholas R Forsyth1*

Author Affiliations

1 Institute for Science and Technology in Medicine, School of Postgraduate Medicine, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK

2 Department of Respiratory Medicine, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire ST4 6QG, UK

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Respiratory Research 2013, 14:9  doi:10.1186/1465-9921-14-9

Published: 25 January 2013

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.

Keywords:
Mesenchymal stem cells; Idiopathic pulmonary fibrosis; Alveolar epithelial wound repair; MSC secretory proteins.