July 27, 2005 Cincinnati scientists have discovered how blood-regenerating stem cells move from bone marrow into the blood stream.
The finding has led to the development of a new chemical compound that can accelerate this process (called stem cell mobilization) in mice--which could eventually lead to more efficient stem cell harvesting for human use.
The researchers, from the Cincinnati Children's Hospital Medical Center and the University of Cincinnati (UC), studied the migration of mouse stem cells to better understand how adult cells move into the bone marrow during stem cell transplants--or can be directed into the blood stream, where they can be more easily harvested for use in transplant procedures.
The team, led by Jose Cancelas, MD, PhD, and David Williams, MD, found that a group of proteins known as the RAC GTPase family plays a significant role in regulating the location and movement of stem cells in bone marrow.
Dr. Cancelas, lead author of the report, is director of research at UC's Hoxworth Blood Center. Dr. Williams, the senior author, heads experimental hematology at Cincinnati Children's.
The researchers discovered that by inhibiting RAC GTPase activity in mice, they were able to "instruct" stem cells to move from their home in the bone marrow and into the blood stream, where they can easily be collected. They achieved this using a drug, developed by Cincinnati Children's faculty member Yi Zheng, PhD, known as NSC23766.
Their findings are reported in the Aug. 6 edition of the scientific journal Nature Medicine.
Scientists have long known that bone marrow stem cells regenerate blood cells. Recent research has also suggested that these cells may help repair damage in other organs, such as the heart and brain.
Injected during transplants procedures, stem cells migrate to a specific location in the bone marrow, where they reestablish the mechanism of blood formation.
"Our findings demonstrate that RAC GTPase proteins are essential for injected stem cells to migrate into the correct location in the bone marrow," said Dr. Williams.
Researching the location of and the factors involved in stem cell regeneration is important to the development of new therapeutic tools in stem cell therapy, said Dr. Cancelas, lead author of the report.
"We wanted to know why stem cells are located in specific pockets of the bone marrow," he said, "and how can they be mobilized to move into the blood stream for easier collection."
Adult stem cell transplantation, or bone marrow transplantation, is used during the treatment of cancer and genetic blood diseases, such as sickle cell anemia, to restore blood cell formation in bone marrow that has been damaged by high-dose chemotherapy or radiation therapy. It has also shown promise in animal studies for possible treatment of organ damage, such as that seen in heart disease and degenerative diseases like Parkinson's.
During high-dose radiation therapy treatment, given to kill advanced cancer, normal stem cells found in bone marrow are also destroyed. Without a bone marrow transplant, new blood cells cannot be produced and the patient will die.
When bone marrow or adult stem cells are taken from a matching donor and injected into the patient after radiation or chemotherapy, the cells move through the recipient's blood stream and settle in the same type of tissue they inhabited in the donor.
Although bone marrow is the best known reservoir of stem cells, only one of 100,000 cells in the marrow is a stem cell. There are also small reservoirs of stem cells in other major organs, such as brain, muscle, heart and other tissue.
The research team also included Andrew Lee, Rethinasamy Prabhakar, PhD, and Keith Stringer, MD, PhD. Their work was supported by grants from the National Institutes of Health and the National Blood Foundation.
More than 40,000 bone marrow transplants are performed each year worldwide, about 25,000 using the recipient's own tissue, and 15,000 using tissue from matching donors.
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