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July 6, 2007

Researchers Turn Stem Cells Taken From Fat Tissue Into 'Suicide genes' That Seek Out And Destroy Tumors

cel1.jpgScientists have developed a new gene therapy by using 'suicide genes' derived from mesenchymal stem cells, which search out and kill cancerous tumours.

Mesenchymal stem cells are a well-characterized population of adult stem cells, found in the bone marrow, which can form a variety of cell in the laboratory, including fat cells, cartilage, bone, tendon and ligaments, muscles cells, skin cells and even nerve cells. Mesenchymal stem cells have been studied in great detail and scientists have advanced knowledge about how to grow these cells in culture. Unlike most other human adult stem cells, mesenchymal stem cells can be obtained in quantities appropriate for clinical applications. In the study reported on here, the researchers used fat tissue as the source for mesenchymal stem cell - derived "suicide genes" to attack metastatic tumor cells, 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, ...

... 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 ...

... 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.

Continue reading ...

Related readings:
Adult Stem Cells
Mesenchymal Stem Cells: Isolation and Therapeutics
Stem Cells, Fat Tissue as Routes to Cell-Based Therapy
Stem Cell Review

Posted July 6, 2007 9:45 PM


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