Personalized Therapy for Cancer, Self-Targeting Stem Cell from Fat
American Association for Cancer Research, July 5, 2007
Capable of seeking out tumors and destroying theme like tiny homing missiles, mesenchymal stem cells derived from adipose, or fat tissue, have been engineered by researchers in Slovakia. The modified cells have been called, "suicide genes". In a journal of the American Association for Cancer Research, the July 1 issue of Cancer Research, the Slovakian scientists concluded that this gene therapy approach was a novel way to attack small tumor metastases that evade current detection techniques and treatments.
"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."
By renewing injured cells, mesenchymal stem cells help repair damaged tissue and organs. Solid tumors are also made up of a mix of cancer cells and normal cells, some of which are mesenchymal stem cells. The cells may be able to find both small metastases as well as primary tumors because mesenchymal stem cells are believed to be able to "see" a tumor as a damaged organ and migrate to it. For this reason, researchers believe that the cells can be used as a vehicle for treatment.
The standard therapy for colon cancer is to use a chemotherapy agent called 5-fluorouracil (5-FU), which can produce toxic side effects in normal cells. With this in mind, the researchers worked to find a less toxic way to treat colon cancer with the stem cells they extracted from human fat tissue. The gene cytosine deaminase was inserted into the cell using a retrovirus vector after the mesenchymal stem cells were expanded in a laboratory. A lethal bystander effect can be produced by the gene, which 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.
The researchers injected the engineered mesenchymal stem cells, then 5-FC, into mice with inhibited immune systems who were engrafted with human colon cancer. None of the mice exhibited any signs of toxic side effects while up to a 68.5 percent inhibition of tumor growth was observed in the animals.
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.
The yield of normal mesenchymal stem cells from fat tissue is far greater than when the cells are derived from other sources such as bone marrow.
Altaner said that the, "removal of fat tissue during surgery to remove a tumor would be simple."
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 Slovakian national cancer genomics program supported the study and the League Against Cancer along with the Slovak Academy of Sciences provided grants for funding.