Researchers from the University of Washington School of Medicine have discovered that there is a special microenvironment in the bone marrow that provides nutrition for different types of blood stem cells. This research may one day improve the success rate of stem cell transplantation and chemotherapy. The researchers reported this research work online in the February 24 issue of Nature.

The researchers believe that these findings obtained in mice indicate that it may be possible to therapeutically target Sertoli cells in specific microenvironments. On the one hand, the use of drugs to nourish support cells and promote the positioning of blood stem cells in the bone marrow allows patients undergoing stem cell transplantation to rebuild their immune system more quickly.

On the other hand, it is well known that tumor cells are hidden in the bone marrow. Drugs can be used to destroy this microenvironment and promote cancer cells to enter the bloodstream, making them more susceptible to the effects of chemotherapy.

"Our findings provide hope for targeting these microenvironments to treat specific cancers or to provide stem cell transplant success rates. Currently, we and other researchers are taking the lead in conducting clinical trials to evaluate patients with leukemia or multiple myeloma The possibility of destroying these microenvironments, "said Dr. Daniel Link, senior author of the paper and medical professor.

Using mice, the researchers selectively knocked out a gene known as CXCL12, which is critical for maintaining blood stem cell health. Not all knockout CXCL12 genes in the microenvironment are knocked out, the researchers are targeting specific types of support cells. This led them to find that only certain blood stem cells exist in each microenvironment, and they are nourished by a unique set of supporting cells.

Link said: “The research findings surprised us a lot. There is not only a microenvironment in the bone marrow that forms blood cells. Blood stem cells are precursor cells that fight infection of white blood cells and oxygen-carrying red blood cells. Blood stem cells are in a special microenvironment, while anti-infective blood cells destined to become T cells and B cells are in another environment. "

These findings provide a solid foundation for studying whether destroying these microenvironments can improve the effect of chemotherapy.

In a Phase II preliminary study led by Geoffrey Uy, a medical oncologist and assistant professor of medicine at the University of Washington, Link is evaluating whether the drug G-CSF can alter stem cell microbiota in patients with relapsed or treatment-resistant acute lymphoblastic leukemia surroundings. The drug was approved by the US Food and Drug Administration more than 20 years ago to stimulate white blood cell production in patients undergoing chemotherapy. These patients are often immunocompromised and vulnerable to infection.

In the experiment, patients at the Siteman Cancer Center will receive G-CSF treatment 5 days before chemotherapy. The researchers will determine whether it can destroy the protective environment of the bone marrow microenvironment, making cancer cells more sensitive to chemotherapy.

Although it is too early to know whether this treatment will be successful. Link's new research was supported by another paper published in the same period by Nature. In that study, Sean Morrison, director of the Institute of Children ’s Medical Center at Southwest Texas Medical Center, used a similar molecular method to discover the special microenvironment of blood stem cells in the bone marrow.

Link said: "Now everyone is interested in trying to understand these microenvironments. Both studies provide important information that drives us forward. Next, we hope to understand how we can manipulate the stem cell microenvironment to help accept stem cell transplantation. Of patients. "

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