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Stem cells: Deathly awakening by interferon
February 12, 2009After injuries with blood loss, the body quickly needs to restore the vital blood volume. This is accomplished by a special group of stem cells in the bone marrow. These hematopoietic stem cells remain dormant throughout their lives and are only awakened to activity in case of injury and loss of blood. Then they immediately start dividing to make up for the loss of blood cells. This has recently been shown by a group of scientists headed by Professor Andreas Trumpp of DKFZ.
Dormancy is an important protection mechanism of stem cells. First, it protects their genetic material from genetic alterations, which happen primarily during cell division. In addition, dormancy helps them escape attacks of many cytotoxins, which act only on dividing cells.
Scientists were still puzzling over which signaling molecules actually wake up stem cells from their dormancy. Andreas Trumpp and Marieke Essers from his team have now reported in Nature that interferon-alpha, a messenger substance of the immune system, acts like an alarm clock for hematopoietic stem cells. The scientists have thus shown for the first time that interferon-alpha can have a direct influence on the function of stem cells.
Interferon-alpha is released by immune cells when the organism is threatened by bacteria or viruses. The scientists triggered interferon production in mice by administering a substance that simulates a viral infection to the animals. Subsequently, there was a great increase in the division rate of hematopoietic stem cells. In control animals that were unable to process the interferon signals, the substance did not lead to an awakening of the stem cells.
The investigators obtained further proof of the effect of interferon-alpha using a drug called 5-fluorouracil, a cytotoxic substance frequently used for treating breast or bowel cancer. Dormant stem cells are resistant to the drug, which unfolds its effect only during division. However, if animals are given interferon-alpha prior to treatment with 5-fluorouracil, they die of anemia after a short time. This is because prior treatment with interferon forces quiescent stem cells into cell division, which sensitizes them for the effect of 5-FU and kills them. Thus, there are soon no more stem cells to keep up the supply of short-lived mature blood cells such as erythrocytes and blood platelets.
What researchers find particularly exciting about this finding is the prospect that the newly found working mechanism might help improve cancer treatment: "Using interferon-alpha, we might be able to wake up from dormancy not only hematopoietic stem cells but also tumor stem cells and, thus, break their frequently observed resistance to many anticancer drugs," Andreas Trumpp speculates.
A clinical observation already suggests that this assumption is more than just wishful thinking: Patients suffering from a type of blood cancer called chronic myelogenous leukemia who are treated with a drug called Gleevec almost always relapse after drug treatment has ended. Several patients were given interferon-alpha prior to the Gleevec treatment. Surprisingly, these patients experienced long relapse-free phases without any medication. "We believe that the leukemia stem cells were awakened by the interferon administration and, thus, were sensitized to elimination by Gleevec," Andreas Trumpp explains.
Helmholtz Association of German Research Centres
Interferon-alpha is released by immune cells when the organism is threatened by bacteria or viruses. The scientists triggered interferon production in mice by administering a substance that simulates a viral infection to the animals. Subsequently, there was a great increase in the division rate of hematopoietic stem cells. In control animals that were unable to process the interferon signals, the substance did not lead to an awakening of the stem cells.
The investigators obtained further proof of the effect of interferon-alpha using a drug called 5-fluorouracil, a cytotoxic substance frequently used for treating breast or bowel cancer. Dormant stem cells are resistant to the drug, which unfolds its effect only during division. However, if animals are given interferon-alpha prior to treatment with 5-fluorouracil, they die of anemia after a short time. This is because prior treatment with interferon forces quiescent stem cells into cell division, which sensitizes them for the effect of 5-FU and kills them. Thus, there are soon no more stem cells to keep up the supply of short-lived mature blood cells such as erythrocytes and blood platelets.
What researchers find particularly exciting about this finding is the prospect that the newly found working mechanism might help improve cancer treatment: "Using interferon-alpha, we might be able to wake up from dormancy not only hematopoietic stem cells but also tumor stem cells and, thus, break their frequently observed resistance to many anticancer drugs," Andreas Trumpp speculates.
A clinical observation already suggests that this assumption is more than just wishful thinking: Patients suffering from a type of blood cancer called chronic myelogenous leukemia who are treated with a drug called Gleevec almost always relapse after drug treatment has ended. Several patients were given interferon-alpha prior to the Gleevec treatment. Surprisingly, these patients experienced long relapse-free phases without any medication. "We believe that the leukemia stem cells were awakened by the interferon administration and, thus, were sensitized to elimination by Gleevec," Andreas Trumpp explains.
Helmholtz Association of German Research Centres
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Vectors derived from retroviruses are useful tools for long-term gene transfer because they allow stable integration of transgenes and propagation into daughter cells.
Comprehensive look at rare leukemia finds relatively few genetic changes launch disease
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Human term placenta a new abundant source of hematopoietic cells
Investigators at Children's Hospital Oakland Research Institute, Oakland, California found a way to obtain large numbers of hematopoietic stem cell from human term placenta.
What do blood stem cells need to grow? Blood flow
Blood stem cells literally go with the flow, according to a new report published as an immediate early publication in the journal Cell, a Cell Press journal, on May 13th.
World premiere in stem cell research in Montreal
A team from the Institute for Research in Immunology and Cancer (IRIC) at Université de Montréal has succeeded in producing a large quantity of laboratory stem cells from a small number of blood stem cells obtained from bone marrow.
Scientists identify key gene that protects against leukemia
Researchers have identified a gene that controls the rapid production and differentiation of the stem cells that produce all blood cell types-a discovery that could eventually open the door to more streamlined treatments for leukemia and other blood cancers, in which blood cells proliferate out of control.
Scientists uncover indicator that warns leukemia is progressing to more dangerous form
Scientists at the Moores Cancer Center at the University of California, San Diego, Stanford University School of Medicine and other centers have identified a mechanism by which a chronic form of leukemia can progress into a deadlier stage of the disease.
Research shows cell's inactive state is critical for effectiveness of cancer treatment
A new study sheds light on a little understood biological process called quiescence, which enables blood-forming stem cells to exist in a dormant or inactive state in which they are not growing or dividing.
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