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Researcher found that modulating blood-forming stem cells'
stiffness could possibly facilitate mobilization procedures
used for stem cell-based transplants. Temporary squishiness
could help drive blood-forming stem cells out of the bone
marrow and into the blood, but the cells need to be stiff to
stay put and replenish the blood and immune system. The
research provides insights into how alterations in blood
stem cell biomechanics can be associated with certain blood
disorders, including leukemia’s. “Bone marrow transplants,"
as part of a treatment strategy for cancer, don't usually
involve physically extracting bone marrow. Instead, doctors
use a drug (G-CSF) that encourages blood-forming stem cells
to leave the bone marrow and enter the blood, because it
generally gives a higher yield. However, that is not the
case for about a third of patients, for whom mobilization is
insufficient. Researcher generated mice without Ptpn21, and
in the bone marrow of the mutant mice. There were fewer stem
cells and early progenitor cells. In addition, blood-forming
stem cells tended to be further away (twice as far) from the
niches where usually reside. The mutant mice were very
sensitive to chemotherapy drugs, but it was also easier to
spur blood stem cells out of their bone marrow. These
observations suggested deformability as an explanation.
Blood stem cells from mutant mice could more easily squeeze
through narrow pores. The Ptpn21-mutant cells were indeed
squishier, and the scientists were able to measure exactly
how much. Qu’s lab performed additional experiments to pin
down how the loss of Ptpn21 affects cell deformability. In
addition, researcher showed that treating normal mice with
blebbistatin, which interferes with parts of a cell's
internal skeleton, also results in mobilization of stem
cells into the blood. In addition, researcher findings
suggest that cell biomechanics can be leveraged to improve
current mobilization regimens for stem cell-based therapy.
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