Fat Kills Cancer: Turning Stem Cells Taken from Fat Tissue into
Personalized, Cancer-Targeted Therapeutics
Researchers in Slovakia have been able to derive mesenchymal stem
cells from human adipose, or fat, tissue and engineer them
into "suicide genes" that seek out and destroy tumors like tiny
homing missiles. This gene therapy approach is a novel way to attack
small tumor metastases that evade current detection techniques and
treatments, the researchers conclude in the July 1 issue of Cancer
Research, a journal of the American Association for Cancer Research.
Newswise — Researchers in Slovakia have been able to derive
mesenchymal stem cells from human adipose, or fat, tissue and
engineer them into "suicide genes" that seek out and destroy tumors
like tiny homing missiles. This gene therapy approach is a novel way
to attack small tumor metastases that evade current detection
techniques and treatments, the researchers conclude in the July 1
issue of Cancer Research, a journal of the American Association for
Cancer Research.
"These fat-derived stem cells could be exploited for personalized
cell-based therapeutics," said the study's lead investigator, Cestmir
Altaner, Ph.D., D.Sc., an associate professor in the Cancer Research
Institute of the Slovak Academy of Sciences in Bratislava. "Nearly
everyone has some fat tissue they can spare, and this tissue could be
a source of cells for cancer treatment that can be adapted into
specific vehicles for drug transport."
Mesenchymal stem cells help repair damaged tissue and organs by
renewing injured cells. They are also found in the mass of normal
cells that mix with cancer cells to make up a solid tumor.
Researchers believe mesenchymal stem cells "see" a tumor as a damaged
organ and migrate to it, and so might be utilized as a "vehicle" for
treatment that can find both primary tumors and small metastases.
These stem cells also have some plasticity, which means they can be
converted by the micro environment of a given tissue into specialized
cells, Altaner says.
After extracting the stem cells from human fat tissue the researchers
worked to find a less toxic way to treat colon cancer than the
standard-of-care chemotherapy agent, 5-fluorouracil (5-FU), which can
produce toxic side effects in normal cells. They expanded the number
of mesenchymal stem cells in the laboratory and then used a
retrovirus vector to insert the gene cytosine deaminase into the
cell. This gene can convert a less toxic drug, 5-fluorocytosine (5-
FC), to 5-FU inside the stem cells, and the chemotherapy can then
seep out into the tumor, producing a lethal by-stander effect.
In nude mice – animals with an inhibited immune system – engrafted
with human colon cancer, the researchers first injected the
engineered mesenchymal stem cells, then 5-FC. They found tumor growth
was inhibited by up to 68.5 percent in the animals, and none of the
mice exhibited any signs of toxic side effects.
However, none of the animals remained tumor-free. "The procedure was
quite effective even though we applied the stem cells just once.
Obviously, repeated treatment will increase the efficacy, as would
using this strategy in combination with other treatments," Altaner
said.
Normal mesenchymal cells can be isolated from various sources,
including bone marrow, but the yield is not nearly as great as what
the researchers derived from fat tissue. Removal of fat tissue during
surgery to remove a tumor would be simple, says Altaner. Liposuction
could also be used to isolate mesenchymal stem cells can also be
gathered and isolated through liposuction, and the cells frozen in
liquid nitrogen for future therapeutic use. Both processes would be
easier than taking bone marrow from a patient, Altaner said.
The study was funded by grants from the Slovak Academy of Sciences
and the League Against Cancer, and support from the Slovakian
national cancer genomics program.
The mission of the American Association for Cancer Research is to
prevent and cure cancer. Founded in 1907, AACR is the world's oldest
and largest professional organization dedicated to advancing cancer
research. The membership includes nearly 26,000 basic, translational,
and clinical researchers; health care professionals; and cancer
survivors and advocates in the United States and more than 70 other
countries. AACR marshals the full spectrum of expertise from the
cancer community to accelerate progress in the prevention, diagnosis
and treatment of cancer through high-quality scientific and
educational programs. It funds innovative, meritorious research
grants. The AACR Annual Meeting attracts more than 17,000
participants who share the latest discoveries and developments in the
field. Special Conferences throughout the year present novel data
across a wide variety of topics in cancer research, treatment, and
patient care. AACR publishes five major peer-reviewed journals:
Cancer Research; Clinical Cancer Research; Molecular Cancer
Therapeutics; Molecular Cancer Research; and Cancer Epidemiology,
Biomarkers & Prevention. Its most recent publication, CR, is a
magazine for cancer survivors, patient advocates, their families,
physicians, and scientists. It provides a forum for sharing
essential, evidence-based information and perspectives on progress in
cancer research, survivorship, and advocacy.
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