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Why it is difficult to produce large numbers of same type cells in lab


April 1, 2011 - Washington

Researchers have provided another piece in the puzzle of why it can be so hard to produce large numbers of the same type of cell in the lab - a process that is vital for scaling up stem cell production for therapeutic use.

This knowledge will help researchers to develop strategies for obtaining the desired cell type for use in either research or medicine.

The study showed for the first time that a gene called Sox10 coordinates a vital part of healthy development: once a stem cell has committed to becoming a neuron it sends out a signal telling surrounding cells to become something else - a characteristic that certainly hinders making pure samples of these cells for therapies.

"We've known for a while that Sox10 is important for healthy development - in fact mutations in Sox10 cause some rare human diseases - but this is the first time it has been shown to help achieve the balance of neurons and glia, the cells that support neurons," said Robert Kelsh from the University of Bath.

Mutations in Sox10 are associated with Waardenburg syndrome - a rare inherited condition causing deafness and reduced hair, skin and eye pigment - and Hirschsprung's disease, which occurs as a result of incomplete development of nerves in the large intestine and leads to severe digestive problems.

"Often when you produce stem cells in the lab, you want them to take on a particular set of characteristics - say, those of a nerve cell. But it can be really difficult to get 100 pc of cells that are the same - there are often a significant minority of cells with other characteristics. We think this might be because inside an animal it is crucial that stem cells generate the right numbers of the right types of cells and in the right locations, and there are mechanisms that ensure this is the case," said Kelsh.

"Encouraging a cell down one route in the lab may well trigger activation of these balancing mechanisms, and thus act to limit the proportion of cells that go down this route. For this reason, understanding the mechanisms generating this balance is crucial," he added.

Kelsh and his team have used Zebrafish to study one of these intermediate stages in a developing organism and not just in a petri dish.

They have discovered that Sox10 helps to coordinate the discussion between neighbouring stem cells to ensure that a balance is struck, and all cell-types are represented in the right proportions.

Inside the Zebrafish this helps in the regulation of healthy development by ensuring that neurons are formed alongside appropriate numbers of their support cells that allow them to function properly.

The finding is being presented at the UK National Stem Cell Network annual science conference.

ANI

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