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Researchers in Slovakia have been able to derive mesenchymal stem cells from human adipose tissue and engineer them into 'suicide genes' that seek out and destroy tumours like tiny homing missiles.
This gene therapy approach is a novel way to attack small tumour metastases that evade current detection techniques and treatments, the researchers said. The paper is published in Cancer Research, a journal of the American Association for Cancer Research.
"These fat-derived stem cells could be exploited for personalised cell-based therapeutics," the study's lead investigator, Associate Professor Cestmir Altaner from the Cancer Research Institute of the Slovak Academy of Sciences in Bratislava, said.
"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 tumour.
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 tumour, producing a lethal bystander 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 tumour growth was inhibited by up to 68.5 per cent in the animals, and none of the mice exhibited any signs of toxic side effects.
However, none of the animals remained tumour-free. "The procedure was quite effective even though we applied the stem cells just once," Altaner said.
"Obviously, repeated treatment will increase the efficacy, as would using this strategy in combination with other treatments."
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 tumour would be simple, Altaner said.
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, he said.
Source: American Association for Cancer Research
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