Stem Cells Have GPS to Generate Proper Nerve Cells

OneIndia, May 12, 2010

One of the main questions in stem cell therapy is how the injected cells "know" to find their way into the specific parts of the body where they are needed. The most common example of stem cells homing is during bone marrow transplant. In this situation donor stem cells are administered to the recipient intravenously, but somehow they find their way to the bone marrow of recipient, and once in the bone marrow start producing new blood cells. It was discovered that specific cells in the bone produce a chemical signal called stromal derived factor (SDF)-1 that acts as a homing beacon for the stem cells, causing them to be localized in the bone marrow regardless of where they are injected. This is explained in the video www.youtube.com/watch?v=VJaQkYWdJ8w.

By knowing the signals involved in keeping stem cells in the bone marrow, drugs have been made that can temporarily release them from the bone into circulation. One example of such a drug made by Genzyme called Mozibil. This is a small molecule that has been synthesized to act as an agent that blocks the interaction between SDF-1 and its receptor. By blocking this interaction, stem cells are "mobilized" to exit the bone marrow and enter systemic circulation. Once the drug exits circulation by normal metabolism, the stem cells home back to the bone marrow, or if there is injury in the body, some of them localize to the damaged area.

Mozibil and similar agents are useful in situations where one wants to collect patient stem cells without having to perform a bone marrow aspiration, which is a painful procedure involving drilling numerous holes in the bone of the donor. Another use of such "mobilizers" is to increase the number of stem cells in circulation, to accelerate recovery in conditions such as stroke or heart attack. In both of these conditions an increase in circulating stem cells is associated with better recovery. Thus if one artificially increases the number of stem cells in circulation by administering agents such as Mozibil, it may be possible to see a therapeutic benefit.

While the control of stem cell homing for the bone marrow is relatively well-known, the brain is a completely different matter. A previously unknown factor that regulates how stem cells produce different types of cells in different parts of the nervous system has been discovered by Stefan Thor, professor of Developmental Biology, and graduate students Daniel Karlsson and Magnus Baumgardt, at Linköping University in Sweden.

The scientists studied a specific stem cell in the nervous system of the fruit fly. This stem cell is present in all segments of the nervous system, but outside of the nervous system it is found only in the thorax. To investigate why this cell type is not created in the stomach or head region they manipulated the Hox genes' activity in the fly embryo. The investigators found out that the Hox genes in the stomach region stop stem cells from splitting before the specific cells are produced. In contrast, the specific nerve cells are actually produced in the head region, but the Hox genes turn them into another, unknown, type of cell. Hox genes can thus exert their influence both on the genes that control stem cell division behaviour and on the genes that control the type of nerve cells that are created.

"We constantly find new regulating mechanisms, and it is probably more difficult than previously thought to routinely use stem cells in treating diseases and repairing organs, especially in the nervous system", says Thor.

The regulation of stem cell homing by Hox genes has previously been demonstrated in other systems, however this is the first time that it was found in relation to development of the nervous system. These findings may lead to strategies for "rewiring" neurons after injury has occurred in situations such as cerebral palsy or stroke.