A new finding published in January of 2011 showed another discovery in stem cell research that can increase the success rate of bone marrow transplant for patients suffering from chronic lymphocytic leukemia and other blood-related malignancies.
The study was undertaken in Santa Cruz, California, by researchers in the University of California. It all boils down to the discovery of one molecule they call : the Robo4. This molecule is actually the key molecule for the development of blood stem cells in their niche inside the bone marrow. The conclusions, published in the January issue of Cell Stem Cell, could contribute to improvements in the safety and success rates of bone marrow transplants.
Actually, a bone marrow transplant is a form of stem cell therapy. This technique is used to treat cancers such as leukemia and lymphoma as well as other blood-related illnesses. In the bone marrow transplant, the “valued element” are blood stem cells, these are seen in the bone marrow and eventually develop to all the varied forms of mature blood cells. Now where does the molecule that we were talking a while ago fit in? Findings of the research shows that blood stem cells use a molecule called Robo4 to anchor themselves in the bone marrow. Now you guessed it right, if the hematopoietic stem cells are securely attached to the bone marrow, being nurtured as it grows, the better are the chances that it will successfully develop into mature blood cells later on.
Camilla Forsberg, an assistant professor of biomolecular engineering in the Baskin School of Engineering at UC Santa Cruz says, “Robo4 is a rare molecule that is found only in hematopoietic stem cells and in the endothelial cells of blood vessels.” After prior investigations in her laboratory reveled that Robo4 is specific for blood stem cells, C. Forsberg would want to know its role.
The findings show that the blood stem cells need Robo4 for it to remain in the bone marrow, so this molecule has potential therapeutic implications. An increasingly common alternative to conventional bone marrow transplants (which needs anesthesia for the bone marrow extraction) involves extracting hematopoietic stem cells from the blood. Scheduled injections of drugs are routine to get the stem cells to leave the bone marrow and enter the bloodstream so that they can be harvested with a blood draw. A drug that blocks Robo4 could be a safer and more effective procedure for this, Forsberg added.
“If we can get specific and efficient inhibition of Robo4, we might be able to mobilize the hematopoietic stem cells to the blood more efficiently,” Forsberg said. “We’re already working on that in the second phase of the project.”
Robo4 acts as the binding molecule, and does it’s work within the bone marrow to keep the stem cells into their proper niche. Moreover, Forsberg’s team is attempting to discover and isolate the missing link – which is the molecules bind to Robo4. This can lead to a better understanding of that niche. While other forms of stem cells are routinely grown in the laboratory, blood stem cells are extremely hard to reproduce in petri dishes, as these stem lines need the environment to closely resemble the bone marrow environment as much as possible for it to be successfully grown. Because of the good outcome in Forsberg’s research, her team might help other scientists to pattern that environment in a petri dish.
Molecules other than the Robo4 are also found to be involved in helping the localization of hematopoietic stem cells in the bone marrow. Forsberg’s conclusions show that one of these, called Cxcr4, acts along with Robo4 to keep blood stem cells in the bone marrow. But the two molecules seem to act through different molecular mechanisms. Inhibition of these two molecules may be the ideal way to have efficient mobilization of hematopoietic stem cells, Forsberg added.
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