Stem cell discoveries hold potential to improve cancer treatment
Findings could lead to new ways to fight disease and help patients
recover faster

Date:
January 25, 2022
Source:
Cedars-Sinai Medical Center
Summary:
Recent discoveries by stem cell scientists may help make cancer
treatment more efficient and shorten the time it takes for people
to recover from radiation and chemotherapy.



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


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In the first study, published in the journal Blood, investigators
discovered a protein that is expressed by blood stem cells that could
aid in identifying, studying and deploying the cells for treatments.

"We show that this protein, syndecan-2, identifies primitive blood stem
cells and it regulates stem cell function," said John Chute, MD, director
of the Division of Hematology and Cellular Therapy at Cedars-Sinai and
senior author of the study.

Blood stem cells are found in small quantities 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 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 make
up less than 0.01% of cells in the bone marrow and peripheral blood,
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 tiny number of stem cells that are therapeutic
along with a lot of other cells that are not.

To study this phenomenon, investigators at the Chute laboratory 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 types of cells based 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.



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The researchers found this protein plays an important role in how
hematopoietic stem cells reproduce. When stem cells that express
syndecan-2 were transplanted into mice following irradiation, their cells repopulated. But when stem cells that lacked 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 efficient and less toxic.

Second Discovery The second discovery by Chute and his team -- published
in the journal Nature Communications -- revealed a mechanism through
which the blood vessels in the bone marrow respond to injury, such as
from chemotherapy or radiation.

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

Chute and colleages found that when mice receive radiation treatment,
the cells that line the inner walls of the 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 the investigators blocked the ability of these blood vessel cells
to produce neuropilin 1 or semaphorin 3A, or injected an antibody that
blocks semaphorin 3A communication with neuropilin 1, the bone marrow vasculature regenerated following irradiation. In addition, 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." Termini, a post-doctoral scientist
at the David Geffen School of Medicine at UCLA, was the first author on
both studies.

========================================================================== Story Source: Materials provided by Cedars-Sinai_Medical_Center. Note:
Content may be edited for style and length.


========================================================================== Journal References:
1. Christina M. Termini, Amara Pang, Michelle Li, Tiancheng Fang,
Vivian Y.

Chang, John P. Chute. Syndecan-2 enriches for hematopoietic stem
cells and regulates stem cell repopulating capacity. Blood, 2022;
139 (2): 188 DOI: 10.1182/blood.2020010447
2. Christina M. Termini, Amara Pang, Tiancheng Fang, Martina Roos,
Vivian Y.

Chang, Yurun Zhang, Nicollette J. Setiawan, Lia Signaevskaia,
Michelle Li, Mindy M. Kim, Orel Tabibi, Paulina K. Lin, Joshua
P. Sasine, Avradip Chatterjee, Ramachandran Murali, Heather
A. Himburg, John P. Chute.

Neuropilin 1 regulates bone marrow vascular regeneration and
hematopoietic reconstitution. Nature Communications, 2021; 12 (1)
DOI: 10.1038/s41467-021-27263-y ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220125162426.htm

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