PHOTO: Fused bone marrow cells, shown in blue, were generated when University of Iowa scientists combined cells from two different mouse strains. Fused, or hybrid, cells point to potential ways to develop treatments for degenerative conditions such as heart disease. Credit: University of Iowa.
Cells produced by the approach might also be adapted to treat diseases caused by cell death, such as heart disease and liver failure, the researchers report in the February 2010 print issue of The FASEB Journal.
Based on laboratory studies in test tubes and animal models, the team found, for the first time, that transplanted bone marrow cells not only produce new, healthy bone marrow cells but also can fuse with existing cells in organs such as the kidney and heart. These hybrid cells — part donor, part recipient — do not trigger rejection from the recipient’s immune system and thus may offer ways to protect transplanted organs from rejection.
“Hybrid cells have the advantage of being functional but not stressing the recipient’s immune system. Our findings could improve organ transplantation results and possibly help lead to improved treatments for cancer, autoimmune diseases and non-blood-related degenerative diseases where cells die away or cannot repair themselves,” said Nicholas Zavazava, M.D., professor of internal medicine and director of transplant research at the UI Roy J. and Lucille A. Carver College of Medicine.
The study suggests that when bone marrow cells fuse with certain unhealthy cells in other tissue or organs, the hybrid cells are similar to the original tissue or organ cells, but healthier. This could help explain previous findings by other researchers, Zavazava said, that showed bone marrow transplants can improve heart function in people who had heart attacks. However, using hybrid cells to treat severe non-bone marrow conditions, such as massive heart disease or liver failure, would likely have limitations.
“We found that the cell fusion does not occur at high rate. As a result, using fused, or hybrid, cells for treatment may help small tissue damage but not be sufficient to treat completely the extensive tissue injury that occurs during a massive heart attack,” said Zavazava, who also is a researcher and staff physician with the Iowa City VA Medical Center. “Still, this observation raises the possibility that circulating bone marrow cells could repair injured tissues without us knowing.”
A related part of the study raised interesting questions about cancer treatment, Zavazava said. By combining potential donor and recipient human cells in test tubes in lab experiments, the team found that cancerous cells can fuse with newly transplanted healthy cells. It is not clear, however, whether this happens in actual patients or if it creates problems.
“It’s possible that a remaining cancer cell could fuse with an introduced bone marrow cell and generate a new cancer cell that is more aggressive and thus potentially resistant to treatment,” Zavazava said. “However, this is only an initial finding done in the laboratory, and much more research is needed to determine if this is a problem in any way.”
The study also showed that when bone marrow transplant cells fuse with embryonic stem cell in test tubes, the bone marrow cells become reprogrammed into new embryonic stem cells. The new embryonic stem cells possess genetic material from both fused partners and can be differentiated into other tissues, such as heart cells. However, for potential clinical use, introducing genes into adult cells for reprogramming might be an easier approach, Zavazava said.
The team hopes to learn more about how hybrid cells function, with a long-term goal of improving treatments for degenerative diseases, cancer and autoimmune diseases.
The study was funded in part by support from a VA Merit Review award and a grant from the National Heart, Lung and Blood Institute.
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