SEMINAR: Lung injury and fibrosis: can stem cells deliver regeneration?

Lung injury and fibrosis: can stem cells deliver regeneration?

 

The Seminar: The lung is a remarkable organ with gas exchange and vital immune defence roles accomplished in a branching network of airways and about 200 million alveoli. It is also an extremely dynamic tissue with rapid turnover of lung cells and their surrounding matrix which may explain the ability of new lung tissue regeneration in experimental models of lung growth. Chronic lung diseases such as pulmonary fibrosis and chronic obstructive pulmonary disease are a major cause of illness and an enormous burden on world health systems. Treatment for these diseases is inadequate with patients unresponsive to most current therapies and, despite large programmes in drug discovery, no agents are emerging that can cure or reverse chronic lung diseases. There is hope that cell therapeutic approaches with the regeneration of new lung tissue might be achievable and initial reports using progenitor cells derived from the bone marrow suggest that this approach may ameliorate animal models of lung disease. The mechanism for this action is uncertain but likely depends on paracrine pathways rather than cell engraftment. This presentation reviews some of the milestones in pulmonary fibrosis research and presents data suggesting keratinocyte growth factor delivery in a transgene expressed by stem cells may be effective in preventing animal models of lung fibrosis.

The Speaker: Professor Laurent is currently the Head of the Research Department of Internal Medicine and the Director of the Centre for Respiratory Research at University College London. He directs a team of scientists and physicians conducting research into basic aspects of inflammation and tissue repair and has published over 200 articles in international journals of biomedical research. He was recently awarded the European Respiratory Societies Presidential Award for his contribution to lung science and is currently its head of Science. He is the Editor-in-Chief of the International Journal of Biochemistry and Cell Biology and has edited several books including a four volume Encyclopaedia of Respiratory Medicine. He is a Fellow of the Academy of Medical Sciences and Past- President of the British Association for Lung Research. In June 2012 he takes up a post at the University of Western Australia directing its newly formed Centre for Cell Therapies and Regenerative Medicine

Speaker(s)	Professor Geoff Laurent, Head of the Research Department of Internal Medicine & Director of the Centre for Respiratory Research at University College London, Director of Elect Centre for Cell Therapy and Regenerative Medicine, UWA
Location	Seminar room 1.81 Anatomy, Physiology & Human Biology building north, UWA
Contact	Debbie Hull <debbie.hull@uwa.edu.au> : 6488 3313
Start	Tue, 05 Jun 2012 13:00
End	Tue, 05 Jun 2012 14:00
Submitted by	Debbie Hull <debbie.hull@uwa.edu.au>
Last Updated	Mon, 16 Apr 2012 18:28

 

Ancillary Studies of Lung Stem/Progenitor Cell Epithelial-Mesenchymal Signaling

Ancillary Studies of Lung Stem/Progenitor Cell Epithelial-Mesenchymal Signaling Abstract: Epithelial-mesenchymal signaling is essential for organogenesis and adult tissue maintenance but is poorly understood in lung repair and regeneration. This proposal exploits timely advances by Consortium investigators and the additional skills and resources of collaborating scientists to identify the critical mesenchymal and epithelial stem/progenitor cell populations that mediate lung regeneration and identify the key signaling factors that operate in lung bronchi, bronchioles, and alveoli. Sorted epithelial and mesenchymal cell populations will be scrutinized for evidence of signaling cascade activation separately in both epithelium and mesenchyme. Using murine genetic models and co-cultures of epithelial and mesenchymal cells, prioritized pathways, initially Sonic hedgehog (Shh), will be modulated to establish the role of pathway activation or dysfunction in airway homeostasis and during regeneration. Parallel in vitro models for primary human lung cells will be developed. Additionally, normal and pathologic pathway activation will be assessed in human lung tissue by in situ hybridization and immunohistochemistry. The Aims are: 1) To lineage trace and sort region-specific epithelial progenitor cells and mesenchyme to identify candidate signaling pathways mediating epithelial-mesenchymal crosstalk; 2) To define the role of Shh signaling in epithelial and niche interactions in airway homeostasis and after lung injury; and 3) To employ novel human lung cell in vitro coculture models to test the function of candidate epithelial-mesenchymal signaling pathways identified in mice and to examine expression of cognate molecules in normal and diseased human lung tissues. These studies will exploit the skills, knowledge and tools of the Progenitor Cell Biology Consortium and this Ancillary team and will leverage these assets to enhance our understanding of lung regenerative biology. The information gained will be invaluable for defining mechanisms of normal lung repair and pathologic lung disease development, which lag behind our understanding in cardiac and bone marrow biology and disease. click for more info on lungs repair and regeneration