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Findings could lead to new ways to fight disease and help patients recover faster

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Two recent discoveries by stem cell scientists at Cedars-Sinai could help make cancer treatment more effective and shorten the time it takes for people to recover from radiation and chemotherapy.

In the first study, published in the journal Bloodresearchers have discovered a protein expressed by blood stem cells that could help identify, study and deploy the cells for treatments.

“We show that this protein, syndecan-2, identifies primitive blood stem cells and regulates stem cell function,” said John Chute, MD, director of the division of hematology and cell therapy at Cedars. -Sinai and lead author of the study.

Blood stem cells are found in small amounts in the bone marrow and in peripheral blood – the type that travels through the heart, arteries, capillaries and veins. These stem cells are of interest to scientists because they produce all the blood cells and immune cells in the body. They are used in the curative treatment of people with leukemia and lymphoma.

This approach faces a major challenge: hematopoietic stem cells represent less than 0.01% of bone marrow and peripheral blood cells, and there is not yet a good way to separate them from other cells. This means that when people receive infusions of bone marrow and peripheral blood cells, they get a small number of therapeutic stem cells as well as many other cells that are not.

To study this phenomenon, researchers in the Chute lab led by first author Christina M. Termini, PhD, extracted bone marrow cells from adult mice and ran the samples through a device that can detect hundreds of different cell types. depending on the proteins that live. on their surfaces. This process revealed that hematopoietic stem cells have a high concentration of syndecan-2, which is part of a family of proteins called heparan sulfate proteoglycans, on the cell surface.

Researchers have discovered that this protein plays an important role in the reproduction of hematopoietic stem cells. When stem cells expressing syndecan-2 were transplanted into mice after irradiation, their cells repopulated. But when stem cells lacking syndecan-2 were transplanted, the cells stopped replicating.

By transplanting only cells that express syndecan-2, it may be possible to make blood stem cell transplants more effective and less toxic.

Second discovery

The second discovery by Chute and his team – published in the journal Nature Communication — revealed a mechanism by which blood vessels in the bone marrow respond to injury, such as chemotherapy or radiation therapy.

When people receive radiation or chemotherapy as part of their cancer treatment, their blood counts drop. It usually takes several weeks for these numbers to return to normal levels.

Chute and his colleagues found that when mice receive radiation therapy, cells that line the inside walls of blood vessels in the bone marrow produce a protein called semaphorin 3A. This protein tells another protein, called neuropilin 1, to kill damaged blood vessels in the bone marrow.

When researchers blocked the ability of these blood vessel cells to produce neuropilin 1 or semaphorin 3A, or injected an antibody that blocks communication of semaphorin 3A with neuropilin 1, the bone marrow vasculature regenerated after irradiation. Also, the blood count increased dramatically after a week.

“We discovered a mechanism that appears to control how blood vessels regenerate after injury,” said Chute, lead author of the paper. “Inhibiting this mechanism leads to rapid recovery of blood vessels and blood cells in the bone marrow after chemotherapy or radiation. In principle, targeting this mechanism could allow patients to recover from chemotherapy within one to two weeks, instead of three or four weeks as is currently the case.”

Termini, a postdoctoral researcher at UCLA’s David Geffen School of Medicine, was first author on both studies.