Andreas Trumpp and his colleagues from the German Cancer Research Center have recently spoken about a “silent reserve” of stem cells, wondering what type of medical impact the discovery made in Heidelberg of “dormant stem cells” could have.
Usually, dormant bone marrow cells activate and multiply only in a crisis or emergency to react to serious cellular loss due to a virus or hemorrhage. When their work is done, they return to a dormant stage. This withdrawal phase keeps them protected from mutations, cellular toxins, and other dangerous substances, since the cells do not divide and are not subject to modifications or various types of aggressions.
According to the Trumpp group’s discovery, the dormant reserve can even be recruited artificially using alpha interferon proteins, as reported in Nature magazine (10.1038/nature07815).
This is an important result for various reasons. Alpha interferon is the body’s response to viral attacks on cells. Its release can be an intense, sort of SOS for the cell.
Until now it was thought that it was involved only in the immune system. Instead, Trumpp’s data indicates that it also signals the dormant cells, alerting them of the crisis, and preparing them to intervene. This means that in the bone marrow, it has a function that is entirely different from what occurs at the site of infection. However, if the dormant stem cells are continually stimulated with alpha interferon, they weaken over time. A chronic activation has serious consequences on interferon’s efficiency.
This explains some of the consequences of alpha interferon treatments in hepatitis b, e, and c, which are all illnesses caused by a virus and treated with this protein. Part of the positive effects of alpha interferon could depend on mobilizing supply of stem cells and the renewal of the blood with new cells; it does also have negative effects, including a reduction of platelets and hemoglobin. This is explained by the fact that the stem cell reserve, kept chronically in a state of vigilance, is used up over time.
The results of the researchers from Heidelberg are interesting in chronic myeloid leukemia cases. Trumpp thinks that tumor stem cells function in an analogous way to dormant stem cells of the bone marrow. To eliminate them with cellular toxins, it is first necessary to wake them up with alpha interferon and stimulate them to divide. Trumpp’s thesis is supported by other clinical data. In the past chronic myeloid leukemia was treated with strong doses of proteins, and today with a drug called Glivec. In the majority of patients, if treatment is suspended, the illness returns.
This means that there are cancer cells that are resistant to Glivec. A look at medical records demonstrates that there are some patients in whom the disease does not return when Glivec is interrupted, and previously they were treated with alpha interferon. Trumpp believes that pre-treatment is necessary to definitively remove cancerous stem cells from their cover and and expose them to the cancer killing drugs. A concept which now must be evaluated in clinical experiments.