Stem Cells for Lung Repair in Premature Infants

Bernard Thébaud, M.D., Ph.D.,
Sprott Centre for Stem Cell
Research, Ottawa Hospital
Research Institute

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that follows ventilator and oxygen treatment for acute failure to breath in babies born very prematurely (24-28 weeks of gestation instead of 40). BPD is a major complication of prematurity with a short and long term burden that reach into adulthood. Each year, 10,000 new babies suffer from BPD in the US. The economic burden is estimated at $6 billion/year, representing up to one fourth of all direct pediatric health care costs. Damage to the still developing lung stops the normal growth of the alveoli (the air sacs in the lung that allow the uptake of oxygen and release of waste carbon dioxide). Currently there is no treatment for this disease.

Our body contains stem cells, a pool of cells that can divide indefinitely and, under certain circumstances, have the ability to become any type of cell (i.e. bone, muscle, liver or blood cell, etc.) in the body. These cells are thought to maintain normal organ function and repair small injuries in our body. This is the case for a specific type of stem cell called mesenchymal stromal cell (or MSC). The bone marrow is a well-known source of stem cells, in particular MSCs. Many patients have been treated with MSCs from the bone marrow for various diseases. MSCs can also be found in the umbilical cord blood and umbilical cord tissue of babies. The umbilical cord is a rich source of MSCs with superior healing capabilities compared to adult bone marrow MSCs. The MSC in the umbilical cord can be safely collected and stored without risk for the mother or the baby. This is especially appealing for the treatment of conditions in babies, because the source for their therapy is right there at birth.

Our lab and others around the world have harnessed the healing potential of MSCs to repair lung injury in neonatal mice and rats. In these experimental studies, MSCs were given intravenously or directly into the lung through the airways. MSCs were able to prevent lung injury in these experimental models of BPD. When given right after established lung injury, MSCs derived from cord blood and tissue were able to restore normal lung growth and lung function in neonatal rats. Furthermore, when examined at the age of 6 months (the equivalent of a young adult in humans), the lungs of the rats were still healthy with no adverse effects, suggesting a long lasting effect and safety. These results are very promising and suggest MSCs from the umbilical cord as a potential therapy to prevent or treat BPD and improve the outcome of premature infants. To date, one study treating infants with MSCs from cord blood has been completed in South Korea. Another trial is ongoing in China. The results of these studies are still pending.

Much more needs to be learned about therapies based on MSC from umbilical cord blood and tissue, but experimental studies in the laboratory are very promising and may lead to a new breakthrough treatment for babies born extremely premature.

Dr. Thébaud is a clinician-scientist who is affiliated with the Ottawa Hospital Research Institute, a neonatologist with the Children's Hospital of Eastern Ontario, and a Professor of Pediatrics at the University of Ottawa. Dr. Thébaud obtained his MD at the University Louis Pasteur in Strasbourg, France in 1991 and trained in Pediatrics and Neonatology at the University Paris V in Paris, France, where he also obtained his MSc and PhD, before completing a 2 year post-doctoral fellowship at the University of Alberta. He was recruited to Ottawa in 2012 to accelerate the translation of stem cell-based therapies to improve the outcome of extreme prematurity. Dr. Thébaud led the international team that was the first to demonstrate that stem cells protect and repair the lungs of newborn rats. Dr. Thébaud has over 70 peer-reviewed publications, received the "Rising Star in Perinatal Research" award from the CIHR Institute for Human Development, Child and Youth Health in 2008, and the "Best in Current Canadian Child Health Research" Sanofi Pasteur Research Award in 2007. Dr. Thébaud holds a Tier 2 Canada Research Chair in Lung Development, Injury and Repair.

Reference

• Maria Pierro, Lavinia Ionescu, Tiziana Montemurro, Arul Vadivel, Gaia Weissmann, Gavin Oudit, Derek Emery, Sreedhar Bodiga, Farah Eaton, Bruno Péault, Fabio Mosca, Lorenza Lazzari, & Bernard Thébaud
  Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia
  Published in Thorax doi:10.1136/thoraxjnl-2012-202323