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Stem cell combined with gene therapy repairs damaged tissue in mice

12 October 2009

By Dr Charlotte Maden

Appeared in BioNews 529

A team of scientists at the Massachusetts Institute of Technology (MIT), in Cambridge, US, has found a way of delivering genes into stem cells to ensure they are more effective at their function.

Stem cells are able to rapidly grow into any tissue type, and a major route of investigation is into their use in repairing damaged tissues, such as limbs. Such tests have been relatively unsuccessful, however, since stem cells are not always able to encourage blood vessels into the new tissue, which is necessary to ensure it stays alive. This new approach, says Daniel Anderson, a biomedical engineer at MIT and lead author on the study, 'was an attempt to augment the power of stem cells'.

These researchers used 'nanoparticles' - tiny biodegradable polymers - to carry the human vascular endothelial growth factor (VEGF) gene into stem cells cultured from human bone marrow, and incorporate it into their DNA. They then injected the modified cells into mice with injured hind limbs, and found that the mice had three times the blood vessel density in their limbs compared with mice injected with unmodified stem cells. Four weeks later, only 20 per cent of the mice injected with modified cells had lost their limbs, compared with 60 per cent of mice that received unmodified cells.

Anderson and the researchers are optimistic about the approach, although he notes that 'the precise mechanism by which these nanoparticles deliver DNA is not clear yet'. A concern is that the effect may only be transient; the VEGF levels in the mouse muscle two days after manipulation were significantly raised, but had dropped sharply after four days.

To tackle this problem, viral vectors could be used to transmit genes into stem cells for a more long-term effect. The researchers avoided this technique, however, due to the many risks associated with it, since the virus may integrate into the host genome permanently and activate cancer-causing genes or cause immune reactions.

Duncan Stewart of the Ottawa Hospital Research Institute in Canada says that the work 'represents a proof of principle for gene enhancement strategies'. The new technique will need much further testing and perfecting to address any safety issues before potential tests in humans.

 

SOURCES & REFERENCES
Bloomberg | 05 October 2009
 
The Scientist | 05 October 2009
 
New Scientist | 07 October 2009
 

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