14 DAY TRIAL // University of California, Santa Cruz researchers have found a key molecule that can establish blood stem cells in their niche within the bone marrow, discovery that could significantly improve the safety and efficiency of bone marrow transplants.
Hematopoietic stem cells – the active ingredients of bone marrow that give rise to all the different kinds of mature blood cells, use a molecule called Robo4 to anchor themselves in the bone marrow.
Camilla Forsberg, an assistant professor of biomolecular engineering in the Baskin School of Engineering at UC Santa Cruz, explained that “Robo4 is a rare molecule that is found only in hematopoietic stem cells and in the endothelial cells of blood vessels.”
This is why the researcher decided to find out how Robo4 functions, and discovered that the cells actually need the molecule to stay in the bone marrow.
Robo4 interacts with other components of the bone marrow and acts as an adhesion molecule, binding the stem cells into their proper niche.
To better understand that niche, Forsberg's team is trying to identify the molecules that bind to Robo4.
Most stem cells can be grown in petri dishes, but hematopoietic stem cells are different, being very difficult to grow under lab conditions.
Forsberg said that the hematopoietic stem cells need the bone marrow environment to function correctly, so her research could help scientists recreate that environment in a petri dish.
Growing hematopoietic stem cells artificially is necessary because of the increasingly common alternative to traditional bone marrow transplants – that require anesthesia for the extraction, involves harvesting them from the blood.
In order to get the stem cells to leave the bone marrow and enter the bloodstream before being collected with a blood draw, repeated injections of drugs are necessary.
Forsberg said that a drug that blocks Robo4 could be a safer and more effective way to do this.
“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.
“We're already working on that in the second phase of the project,” she said.
Bone marrow transplants are a necessary therapy for treating cancers like lymphoma and leukemia, as well as other blood-related diseases.
Researchers say that besides, Robo4, there are other molecules that are involved in guiding the localization of hematopoietic stem cells in the bone marrow.
According to Forsberg's results, one of these – Cxcr4, acts together with Robo4 to retain hematopoietic stem cells in the bone marrow, but the two molecules seem to act through different mechanisms.
So the best way to obtain an efficient mobilization of hematopoietic stem cells, could be to inhibit both molecules, concluded Forsberg, whose research is reported in the January issue of Cell Stem Cell.