Hematopoietic stem cells are located in the niche where they are held down by the molecule Robo4  (Source:
Adhesive Robo4 molecule discovery could help researchers create better drug therapies for those with certain cancers

University of California, Santa Cruz, researchers may have found the key to safer and more efficient bone marrow transplants by discovering a molecule that establishes blood stem cells in the bone marrow. 

Camilla Forsberg, study leader and assistant professor of biomolecular engineering in the Baskin School of Engineering at UC Santa Cruz, along with a team of researchers, have found a molecule capable of establishing blood stem cells in their niche in the bone marrow. 

Bone marrow transplants use hematopoietic stem cells to treat blood-related diseases such as leukemia and lymphoma. These hematopoietic stem cells are found within the bone marrow and produce a variety of different mature blood cells. 

Now, Forsberg and her team have discovered a molecule called Robo4, which "anchors" the hematopoietic stem cells in the bone marrow. Robo4 acts as an adhesive, attaching stem cells to their appropriate niche within the bone marrow. 

"Robo4 is a rare molecule that is found only in hematopoietic stem cells and in the endothelial cells of blood vessels," said Forsberg.

A discovery like this could lead to a better understanding of the particular niche that Robo4 resides in while binding the stem cells within the bone marrow. Growing hematopoietic stem cells in a petri dish, like most other stem cells, is extremely challenging because it seems they only function the way they're supposed to when in the actual bone marrow environment. But now, this research may help researchers recreate this environment in a petri dish. 

In addition, this discovery could lead to the development of better drugs for patients who prefer an alternative to conventional bone marrow transplants. For instance, a common alternative is to inject patients with drugs that bring the hematopoietic stem cells out of the bone marrow and into the bloodstream so they can be captured and harvested. This technique requires several injections of the drug to do this, but through the new Robo4 discovery, researchers may be able to create a specialized drug capable of detaching the Robo4 from the stem cells allowing the hematopoietic stem cells to easily flow from the bone marrow to the bloodstream. 

"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," said Forsberg. "We're already working on that in the second phase of the project."

This study was published in Cell Stem Cell.

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