The treatment and recovery process after cancer is also long and painful. Recently, stem cell scientists at Cedars-Sinai have made two very promising discoveries that may help make cancer treatment more efficient and reduce the time it takes people to recover from radiation and chemotherapy.
Researchers have discovered a protein expressed by blood stem cells that could enable the identification, study, and deployment of these cells. The study was published in the journal Blood. “We show that this protein, syndecan-2, identifies primitive blood stem cells and it regulates stem cell function,” said senior author Dr. John Chute of Cedars-Sinai’s Division of Hematology and Cellular Therapy.
There are small amounts of blood stem cells in the bone marrow and in peripheral blood — the type that travels through the arteries, veins, and capillaries. Scientists are interested in these stem cells since they produce all blood cells and immune cells in the body. People with leukemia and lymphoma may receive them as part of a curative treatment.
Although this approach was promising, it was challenged by the fact that hematopoietic stem cells constituted less than 0.01 percent of the cells in the bone marrow and peripheral blood, and there was no good way to separate them from other cells. When patients received infusions of bone marrow or peripheral blood cells, they got a tiny number of therapeutic stem cells along with many nontherapeutic cells.
Using a device that can detect hundreds of types of cells based on the proteins that reside on their surfaces, researchers at the Chute laboratory, led by first author Christina M. Termini, Ph.D., investigated this phenomenon. Syndecan-2, part of the heparan sulphate proteoglycan family, was found to be highly concentrated on the cell surface of hematopoietic stem cells in this process.
Hematopoietic stem cells reproduce by using this protein, according to researchers. After irradiation, cells from mice that were transplanted with syndecan-2 stem cells repopulated. Syndecan-2 is required for cell replication, but the cells stopped reproducing when stem cells lacking the protein were transplanted.
It might be possible to reduce the toxicity and effectiveness of blood stem cell transplants by using only cells that express syndecan-2.
Secondly, Chute and his team discovered a mechanism through which the blood vessels in the bone marrow responded to injury, like that from chemotherapy or radiation. The discovery was published in Nature Communications. Radiation and chemotherapy reduce people’s blood counts as a result of cancer treatment.
Normal counts usually take several weeks to return.
A protein called semaphorin 3A is produced in the bone marrow when mice receive radiation treatment. In the bone marrow, this protein signals neuropilin 1 to kill damaged blood vessels.
Researchers have found that the following irradiation, the bone marrow vasculature regenerated when neuropilin 1 or semaphorin 3A could not produce or communicate with one another. Additionally, blood counts increased dramatically after one week.
“We’ve discovered a mechanism that appears to control how blood vessels regenerate following injury,” said Chute, senior author of the paper. “Inhibiting this mechanism causes rapid recovery of the blood vessels and blood cells in bone marrow following chemotherapy or irradiation. In principle, targeting this mechanism could allow patients to recover following chemotherapy in one to two weeks, instead of three or four weeks as currently experienced.”
(With inputs from ANI)