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Lung Diseases

Lung Disease Research at the McEwen Centre
Background: What is Lung Disease?
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The world’s first single and double lung transplants took place at Toronto General Hospital in 1983 and 1986, respectively (see more World Firsts at www.uhn.ca). This pioneering work has attracted a critical mass of scientists and clinicians who are leading the world in organ transplant, repair and regeneration.

Cellular therapy

Recent studies by Toronto investigators have demonstrated that cell-based therapy may successfully reverse the effects of long-standing obstruction to arteries supplying blood to the lungs. Clinical trials are ongoing at UHN.

• Dr. Thomas Waddell’s team is studying how a special type of bone marrow cells - which express stem cell and lung epithelial cell markers – can help prevent graft rejection by regenerating the airway and modulating the immune response.

• By manipulating airway progenitor cells (from the bone marrow, lung or, in the future from embryonic stem cells), Dr. Waddell is examining the use of these cells as an exciting new approach for cystic fibrosis – “cellular replacement therapy”.

Figure: Transplanted bone marrow cells in an animal model replace the epithelial layer of the airway and form a protective lining (green) that prevents further damage and obstruction of the airway. Credit: Waddell lab

Figure: After manipulation in a test tube, a subset of bone marrow cells express the lung marker CCSP (green) and stem cell marker Sca-1 (red) Credit: Waddell lab

Gene therapy

• Dr. Shaf Keshavjee’s group is investigating gene therapy techniques to genetically modify donor lungs, making them better able to withstand the stress imposed of transplantation.

Tissue engineering

• Dr. Thomas Waddell and Dr. Shaf Keshavjee are working with Dr. Mingyao Liu of UHN to investigate the use of cell-based tissue engineering techniques to regenerate the damaged air pockets in a lung. This early work in animals may help point the way towards using similar strategies to repair damaged human lungs in the future.

Figure: The cell-supplemented biodegradable scaffold can over time form the honeycomb shape airway structures. Arrows point to the border between animal lung and the scaffold. Credit: Dr. Mingyao Liu (in collaboration with Waddell and Keshavjee labs) From Andrade et al., Am J Physiol Lung Cell Mol Physiol. 2007 Feb;292(2)

Figure: New blood vessels are formed in a biodegradable scaffold that was supplemented with bone marrow stem cells and implanted into an animal lung. Credit: Waddell lab.

Background: What is Lung Disease?

Lung diseases affect millions of Canadians and are responsible for thousands of lives lost each year. Several types of lung – or ‘pulmonary’ – disease affect individuals today, including pulmonary hypertension, cystic fibrosis, emphysema, and lung cancer.

Current Therapies for the Treatment of Lung Disease

• Drug Therapy – bronchodilators (asthma), steroids and immunosuppressives (inflammatory lung diseases), or antibiotics (infection)
• Chemotherapy and radiation therapy (lung cancer)
• Surgery or lung transplant

Drug treatments are not always effective and once disease is advanced, transplantation may be the only option. If detected early, lung cancer can be cured by surgery or occasionally radiation, but when advanced, chemotherapy only prolongs survival without cure.

More information on lung disease and current therapies:

• Canadian Lung Association
• American Lung Association
• National Heart Lung and Blood Association
• MedLinePlus – Lung Disease - a Service of the National Institutes of Health and the US Library of Science