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5 big strides to fight lung disease in our tiniest patients

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04.12.2012

For Ottawa scientist and neonatologist Dr. Bernard Thébaud, even a major paper that answers five significant questions still doesn't seem quite enough in his determined path to get his laboratory breakthrough into the neonatal intensive care unit (NICU). Dr. Thébaud's proposed therapy would use stem cells from umbilical cords to treat a disease previously thought to be untreatable — bronchopulmonary dysplasia, or BPD.

These are micro-tomography scans of blood vessels in the lung. Image A shows a normal lung. Image B shows the injury caused by oxygen. Image C shows a lung given oxygen and treated with stems cells from a human umbilical cord.

Credit: Dr. Bernard Thébaud

"BPD is a lung disease described 45 years ago in which we have made zero progress. And now, with these cord-derived stem cells there is a true potential for a major breakthrough," says Dr. Thébaud, a senior scientist at the Ottawa Hospital Research Institute and CHEO Research Institute, a neonatologist at CHEO and The Ottawa Hospital, and a professor in the Faculty of Medicine at the University of Ottawa.

"I am confident that we have the talent and the tools here at CHEO and OHRI to find a treatment for BPD. These findings published today are helping us get there," continues Thébaud.

BPD affects approximately 10,000 very premature newborns in Canada and the U.S. every year. The lungs of these infants are not developed enough to sustain them, so they must receive oxygen through a breathing machine. However, this combination of mechanical ventilation and oxygen damages the lungs and stops their development. In addition, longer stays in the NICU for these extremely premature babies affect the normal development of other parts of the body, including the retina, the kidneys and the brain.

Today in the journal Thorax, Dr. Thébaud's team provides significant findings in experiments with newborn rats given oxygen. The lung development of a newborn rat mimics that of a premature baby born at 24 weeks. The five major findings reported in Thorax are:

- Stem cells called mesenchymal stromal cells (MSCs) from a human umbilical cord (not the blood) have a protective effect on the lungs when injected into the lungs as they were put on oxygen.

- MSCs had a reparative effect when injected two weeks after being on oxygen.

- When conditioned media — a cell-free substance produced by MSCs — was administered instead of MSCs, it was found to have the same protective and reparative effects as the stem cells.

- When examined after six months (the equivalent of 40 human years), treated animals had better exercise performance and persistent benefit in lung structure.

- MSCs did not adversely affect the long-term health of normal rats. One of the concerns about stem cells is that by promoting cell growth, they may cause cancerous growth. To address this question, Dr. Thébaud gave MSCs to a control group that was not treated with oxygen. When examined after six months, these animals were normal and healthy.

Within two years, Dr. Thébaud wants to be talking about a pilot study with 20 human patients showing that this stem-cell therapy is feasible and safe, and in four years he wants to embark on a randomized control trial. These are all steps in his profound desire to help the babies he sees in the NICU with BPD, and he is confident a treatment will be developed.

"It's going to happen here in Ottawa, but for babies worldwide," says Dr. Thébaud.

The full article "Short, Long-term and Paracrine Effect of Human Umbilical Cord-derived Stem Cells in Lung Injury Prevention and Repair in Experimental BPD" was published online first by Thorax on December 4, 2012. This work was a collaborative project with a group in Milano, Italy.

Funding for this study was provided by the Canadian Institutes of Health Research, the Maternal-Fetal Neonatal Training Program sponsored by CIHR's Institute of Human Development, Child and Youth Health, the Alberta Heritage Foundation for Medical Research/Alberta Innovates Health Solutions, the Canadian Foundation for Innovation, the Canada Research Chairs Program, the Stollery Children's Hospital Foundation, the 6FP EU Project – THERCORD and the 7FP EU Project – CASCADE and REBORNE.

Media Contacts
Paddy Moore, OHRI, 613-232-5680 (cell), padmoore@ohri.ca
Adrienne Vienneau, CHEO RI, 613-737-7600 x 4144, 613-513-8437 (cell), avienneau@cheo.on.ca
Néomie Duval, uOttawa, 613-562-5800 x 298, 613-863-7221 (cell), neomie.duval@uottawa.ca

About the Ottawa Hospital Research Institute The Ottawa Hospital Research Institute (OHRI) is the research arm of The Ottawa Hospital and is an affiliated institute of the University of Ottawa, closely associated with the university's Faculties of Medicine and Health Sciences. OHRI includes more than 1,700 scientists, clinical investigators, graduate students, postdoctoral fellows and staff conducting research to improve the understanding, prevention, diagnosis and treatment of human disease. www.ohri.ca.

About the CHEO Research Institute Established in 1984, the CHEO Research Institute coordinates the research activities of the Children's Hospital of Eastern Ontario (CHEO) and is one of the institutes associated with the University of Ottawa teaching hospitals. The Research Institute brings together health professionals from within CHEO to share their efforts in solving pediatric health problems. It also promotes collaborative research outside the hospital with partners from the immediate community, industry and the international scientific world. For more information, please visit www.cheori.org.

About the University of Ottawa The University of Ottawa is committed to research excellence and encourages an interdisciplinary approach to knowledge creation, which attracts the best academic talent from across Canada and around the world. It is an important stakeholder in the National Capital Region's economic development.

Paddy Moore | Source: EurekAlert!
Further information: www.ohri.ca

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