OHSU Research Suggests Compound Administered During Some Bone Marrow Transplants Elevates Risks
09/22/10 Portland, Ore.
G-CSF, a compound used to stimulate stem cell growth prior to transplantation, may also activate a virus that places recipients at increased risk of infection
Research conducted at Oregon Health & Science University’s Vaccine and Gene Therapy Institute may spur debate about the risks associated with administering a specific compound in some forms of bone-marrow transplantation. The research is published in the current edition of Cell Host and Microbe.
The VGTI research team, led by institute director Jay Nelson, Ph.D., studies human cytomegalovirus, a virus that may infect up to 80 percent of the American population. The exact percentage of infected citizens is unknown due to the fact that the virus causes minor symptoms or no symptoms at all in most healthy people. However, the virus can pose a significant risk in people whose immune system has been compromised, such as those infected with HIV, or patients who have had their immune systems suppressed through chemotherapy or with anti-rejection medications during transplantation.
During this specific research project, Nelson, along with M. Shane Smith, Ph.D., a postdoctoral fellow in Nelson’s lab and other colleagues focused on the impact of granulocyte-colony stimulating factor, or G-CSF, on the virus. G-CSF is a hormone frequently administered to bone marrow transplant donors to stimulate stem cell growth and localization of blood prior to harvesting blood-borne stem cells.
While G-CSF-induced stem cell localization to the blood does provide a more comfortable means of stem cell donation compared to the previous method of harvesting cells directly from the bone marrow, previous studies have suggested that bone marrow transplantation performed with blood-borne stem cells places recipients at double the risk for HCMV and chronic graft-versus host disease.
The VGTI research team uncovered the mechanism behind this associated risk. Using a mouse model of the disease, the scientists determined that G-CSF causes HCMV, which is in a dormant or latent state in the bone marrow, to reactivate in stem cells, thereby placing stem cell recipients at elevated risk for HCMV transmission and disease.
“Because bone marrow recipients’ immune systems are so significantly compromised, this risk is very significant,” said Nelson. “We believe this research will generate discussion about the proper applications for G-CSF – which continues to provide benefits – but the risk associated must also be factored into patient care.”
The research was supported by grants from the National Institutes of Health.
Located on the West Campus of OHSU, the Vaccine and Gene Therapy Institute was established in March 2001. The overall mission of the VGTI is to respond to the increasingly serious infectious disease threats facing the people of Oregon, the United States and the world as a whole, including AIDS, chronic viral infection-associated diseases, newly emerging viral diseases, and infectious diseases of the elderly. Vaccine development and the development of novel immune and gene therapeutic approaches to these diseases are the major priorities of the faculty.
Oregon Health & Science University is the state’s only health and research university, and only academic health center. As Portland's largest employer and the fourth largest in Oregon (excluding government), OHSU's size contributes to its ability to provide many services and community support activities not found anywhere else in the state. It serves more than 184,000 patients, and is a conduit for learning for more than 3,900 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to each county in the state.