Stems Cells Engineered from Fat Fight Cancer

Researchers in Slovakia have been able to derive mesenchymal stem cells from human adipose (fat) tissue and engineer them into "suicide genes” that seek out and kill tumors similar to 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 of the study published their results in the July 1, 2007, issue of the journal 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 (Bratislava, Slovakia). "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 injured tissue and organs by regenerating injured cells. They are also found in the mass of normal cells that mix with cancer cells to comprise 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 microenvironment of a given tissue into specialized cells, according to Dr. Altaner.

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 increased 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 deadly bystander effect.

In nude mice--animals with a suppressed immune system--engrafted with human colon cancer, the researchers first injected the engineered mesenchymal stem cells, then 5-FC. They discovered that tumor growth was suppressed by up to 68.5% 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,” Dr. 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, according to Dr. Altaner. Liposuction could also be used to isolate mesenchymal stem cells, which then can also be collected 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, according to Dr. Altaner.


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Slovak Academy of Sciences