In laboratory studies, Johns Hopkins researchers say
they have found that stem cells from a patient’s own
fat may have the potential to deliver new treatments
directly into the brain after the surgical removal
of a glioblastoma, the most common and aggressive
form of brain tumor.
The investigators say so-called mesenchymal stem
cells (MSCs) have an unexplained ability to seek out
damaged cells, such as those involved in cancer, and
may provide clinicians a new tool for accessing
difficult-to-reach parts of the brain where cancer
cells can hide and proliferate anew. The researchers
say harvesting MSCs from fat is less invasive and
less expensive than getting them from bone marrow, a
more commonly studied method.
Results of the Johns Hopkins proof-of-principle
study are described online in the journal PLOS ONE.
"The biggest challenge in brain cancer is the
migration of cancer cells. Even when we remove the
tumor, some of the cells have already slipped away
and are causing damage somewhere else," says study
leader Alfredo Quinones-Hinojosa, M.D., a professor
of neurosurgery, oncology and neuroscience at the
Johns Hopkins University School of Medicine.
"Building off our findings, we may be able to find a
way to arm a patient’s own healthy cells with the
treatment needed to chase down those cancer cells
and destroy them. It’s truly personalized medicine."
For their test-tube experiments, Quinones-Hinojosa
and his colleagues bought human MSCs derived from
both fat and bone marrow, and also isolated and grew
their own stem cell lines from fat removed from two
patients. Comparing the three cell lines, they
discovered that all proliferated, migrated, stayed
alive and kept their potential as stem cells equally
well.
This was an important finding, Quinones-Hinojosa
says, because it suggests that a patient's own fat
cells might work as well as any to create
cancer-fighting cells. The MSCs, with their ability
to home in on cancer cells, might be able to act as
a delivery mechanism, bringing drugs, nanoparticles
or some other treatment directly to the cells.
Quinones-Hinojosa cautions that while further
studies are under way, it will be years before human
trials of MSC delivery systems can begin.
Ideally, he says, if MSCs work, a patient with a
glioblastoma would have some adipose tissue (fat)
removed – from any number of locations in the body –
a short time before surgery. The MSCs in the fat
would be drawn out and manipulated in the lab to
carry drugs or other treatments. Then, after
surgeons removed the brain tumor, they could deposit
these treatment-armed cells into the brain in the
hopes that they would seek out and destroy the
cancer cells.
Currently, standard treatments for glioblastoma are
chemotherapy, radiation and surgery, but even a
combination of all three rarely leads to more than
18 months of survival after diagnosis. Glioblastoma
tumor cells are particularly nimble, migrating
across the entire brain and establishing new tumors.
This migratory capability is thought to be a key
reason for the low cure rate of this tumor type.
"Essentially these MSCs are like a ‘smart’ device
that can track cancer cells," Quinones-Hinojosa says.
Quinones-Hinojosa says it’s unclear why MSCs are
attracted to glioblastoma cells, but they appear to
have a natural affinity for sites of damage in the
body, such as a wound. MSCs, whether derived from
bone marrow or fat, have been studied in animal
models to treat trauma, Parkinson’s disease, ALS and
other diseases.
This research was supported by the National
Institutes of Health’s National Institute of
Neurological Disorders and Stroke (R01-NS070024),
the Maryland Stem Cell Research Fund and the Howard
Hughes Medical Institute.
Other Johns Hopkins researchers involved in the
study include Courtney Pendleton, M.D.; Qian Li,
Ph.D.; David A Chesler, M.D., Ph.D.; Kristy Yuan,
M.D.; and Hugo Guerrero-Cazares, M.D., Ph.D.
More Information:
http://www.hopkinsmedicine.org/
(MDN)
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