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August 6, 2008

SickKids scientists uncover the key to controlling how stem cells develop

Toronto – Canadian researchers are one step closer to controlling human embryonic stem cell differentiation thanks to the work of scientists Dr. Cheryle Séguin and Dr. Janet Rossant of the Developmental and Stem Cell Biology program at The Hospital for Sick Children (SickKids).

Séguin and Rossant, along with their colleagues Dr. Jonathan Draper of the Stem Cell and Cancer Research Institute at McMaster University , and Dr. Andras Nagy, of Mount Sinai Hospital published these groundbreaking findings in the Cell Press journal, Stem Cell.

Stem cells play a critical role in human development. They are the “master” or “parent” cells from which other cell types are derived. Human embryonic stem cells are seen to be particularly valuable as they are pluripotent, which means that in addition to the having the ability to self-renew, they are also capable of developing into many different kinds of cells in the body. These stem cells provide the starting material for every organ and tissue, and have the potential to develop into each of the more than 200 cell types in the human body—bone, muscle, skin, blood, etc., but are not able to form a complete organism.

One of the biggest hurdles to overcome before the clinical use of embryonic stem cells is our current inability to effectively control the process of stem cell differentiation. While there has been a great deal of research into how to coax human embryonic stem cells into becoming various kinds of cells, this study provides a clear picture of how we might control the early steps of endoderm tissue differentiation.

“Our approach was to basically exploit the cell's own internal control mechanisms to guide differentiation of the cell population as a whole,” says Dr. Séguin, a postdoctoral research fellow at SickKids and the lead author of the study. “By manipulating the expression of transcription factors – how genetic information is communicated within the cell – we were able to understand how to influence to the very essence of the cell fate determination.”

The research team focused on producing early endoderm cells from human embryonic stem cells. Since the endoderm lineage goes on to produce essential organs in the embryo such as the respiratory and digestive tracts, the lung, liver and pancreas, research was directed towards generating stable progenitor cells capable of producing all endoderm cell types. These cells were able to maintain their distinct profiles through many stages of cell culture without losing their ability to self renew.

“We believe that this process provides new tools to explore the pathways of endoderm differentiation,” comments Dr. Rossant, Chief of Research at SickKids. “We tried to make the most "immature" cell types of two different lineages of cells in the early embryo . This way we establish a stable starting population of cells and try to guide them through the next steps that are required to differentiate into the mature cell types that make up various organs.”

While this new understanding will not yet lead to use of embryonic stem cells in human patients, this is an important step in the process. Having a better understanding of how we manipulate cells to control how they differentiate is an important leap and in the future will lead us into new pathways in regenerative medicine. By studying stem cells that carry DNA with disease-causing mutations, researchers may soon learn more about how these mutations cause the cell to become diseased. This will also lead to research into generating new drugs or therapies that are able to directly address the genetic defect and treat the disease.

This research was supported by the Canadian Institutes of Health Research, the Stem Cell Network, the Natural Sciences and Engineering Research Council of Canada, the Juvenile Diabetes Research Foundation, the Biotechnology and Biological Sciences Research Council UK, and SickKids Foundation.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada's most research-intensive hospital and the largest centre dedicated to improving children's health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca . SickKids is committed to healthier children for a better world.

For more information, please contact:

Janice Nicholson
Public Affairs
The Hospital for Sick Children
Phone: 416-813-6684
Fax: 416-813-5328
email: janice.nicholson@sickkids.ca