August 31, 1998
Discovery of new stem cell leads to better understanding of blood system, and raises questions about current methods used for human stem cell transplants
TORONTO - A team of researchers, led by SickKids geneticist John Dick, PhD, at The Hospital for Sick Children, has discovered a new stem cell in human blood providing researchers with further insight into the working of the blood system. The discovery also questions whether current methods for human stem cell transplants used in the treatment of some blood diseases need to be modified. This discovery will enable the development of new treatments, including gene therapy for blood diseases such as leukemia, thalassemia and sickle cell anemia. The work is published in the August 31 issue of Nature Medicine.
Scientists have proven that stem cells are the source from which the entire blood system is derived. Currently, many human stem cell transplants take advantage of the presence of a protein marker on the surface called CD34. For example, in a cancer patient, bone marrow or blood is taken and the cells that have CD34 on their surface are selected for transplantation while the rest of the cells (that contain non-stem cells and cancer cells) are thrown away. The CD34 selected stem cells are transplanted back into the cancer patients after they receive a near-lethal dose of chemo therapy to kill the cancer cells. The transplanted stem cells will regrow the blood system destroyed by the cancer treatment.
The newly discovered stem cells are different. They do not express the CD34 marker. As a result, the new stem cells are often discarded in current transplantation methods. These stem cells grow differently in lab cultures, and have different functions that may provide a target for stem cell gene therapy. This new finding has only been shown in animal models, researchers will now attempt to determine it's significance for human patients.
"The identification of this new type of stem cell is important biologically in order to understand how the blood system works. It is important clinically because we may be able to make stem cell transplants better and develop new therapies if we focus on this new stem cell," says Dr. Dick, who is also professor of Molecular and Medical Genetics at The University of Toronto.
Research focused over the past few years has been looking into the functions of stem cells, which make up just one in a million bone marrow cells. The problem with studying stem cells has been that they look like any other bone marrow cell under the microscope. The only way to tell the difference is to see them in action in a living organism as they produce bone marrow cells. In humans, the only time this is clearly visible is following bone marrow transplantation. Given this, stem cell research involving humans is impossible.
In order to study the entire human blood system and how this system develops from stem cells, Dr. Dick's research team over the last 10 years has developed a biological system and successfully reproduced the entire human blood system in mice. By transplanting human blood cells into special immune-deficient mice called NOD/SCID mice, this system provides scientists with a living organism in which to study the development of the human blood system.
Stem cell transplants are now widely used for treating different types of cancer, anemias and auto-immune disorders.
The research team includes former SickKids post-doctoral fellows Dr. Mick Bhatia, (now principal investigator, Robarts Research Institute, London, Ontario), Dr. Dominique Bonnet and research associate Olga Gan and technician Barbara Murdoch.
Funding for this research was provided by the Medical Research Council of Canada, the Canadian Genetic Diseases Network of the Centers of Excellence and the National Cancer Institute of Canada with funds from the Canadian Cancer Society.
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