01 February 2022

Two discoveries could help to make stem cell treatment more efficient and shorten the time it takes for people to recover from radiation and chemotherapy, researchers have announced.

Scientists at Cedars-Sinai Medical Center, Los Angeles, California, USA, have found that syndecan-2 identifies primitive blood stem cells and regulates stem cell function.

People who receive stem cell transplants (either from bone marrow or peripheral blood) get a mixture of therapeutic and non-therapeutic cells. Researchers continue to search for ‘markers’ which identify a pure population of long-term haematopoietic stem cells from a donor which can repopulate the recipient’s blood system.

Writing in the journal Blood, a team led by Dr John Chute extracted bone marrow cells from adult mice and ran the samples through a device that detects hundreds of different types of cells based on the proteins on their surfaces.

This revealed that long-term hematopoietic stem cells have a high concentration of syndecan-2, which is part of the heparan sulfate proteoglycans family of proteins, on the cell surface. Conversely, syndecan-2-positive haematopoietic stem cells were highly enriched for cells capable of long-term haematopoietic reconstitution. 

They found when stem cells that express syndecan-2 were transplanted into mice following irradiation, their cells repopulated. When stem cells that lacked syndecan-2 were transplanted, the cells stopped replicating.

This means by transplanting only cells that express syndecan-2, it could be possible to make blood stem cell transplants more efficient and less toxic, the researchers say.

Chute and his team published a related discovery in Nature Communications. This revealed a mechanism through which the blood vessels in the bone marrow respond to injury, including from chemotherapy or radiation.

When people receive radiation or chemotherapy as part of their cancer treatment, their blood counts fall dramatically. It can take several weeks for these counts to return to normal levels.

In experiments with mice receiving radiation treatment, the team found the cells that line the inner walls of the blood vessels in the bone marrow produce the semaphorin 3A protein. This tells another protein, neuropilin 1, to instruct damaged blood vessels in the bone marrow to self-destruct.

However, when the researchers blocked this interaction – either by blocking the blood vessel cells from producing neuropilin 1 or semaphorin 3A, or by injecting an antibody that blocks semaphorin 3A communication with neuropilin 1 – the bone marrow vasculature regenerated following irradiation much quicker.

Blood counts also increased dramatically after one week, they found.

“We've discovered a mechanism that appears to control how blood vessels regenerate following injury,” said Dr Chute. “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.”

Source:

Termini CM, Pang A, Li M, Fang T, Chang VY, Chute JP. (2022) “Syndecan-2 enriches for hematopoietic stem cells and regulates stem cell repopulating capacity.” Blood, doi: 10.1182/blood.2020010447

Link: https://ashpublications.org/blood/article/doi/10.1182/blood.2020010447/476854/Syndecan-2-expression-enriches-for-hematopoietic

Termini CM, Pang A, Fang T, Roos M, Chang VY, Zhang Y, Setiawan NJ, Signaevskaia L, Li M, Kim MM, Tabibi O, Lin PK, Sasine JP, Chatterjee A, Murali R, Himburg HA, Chute JP. (2021) “Neuropilin 1 regulates bone marrow vascular regeneration and hematopoietic reconstitution.” Nature Communications, doi: 10.1038/s41467-021-27263-y

Link: https://www.nature.com/articles/s41467-021-27263-y

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