Adult stem cells hold promise in future MS therapy

By Susan Williamson
Tuesday, 21 January, 2003

Researchers at Sydney's St Vincent's Hospital have found for the first time that adult stem cells can be differentiated into the white matter forming cells of the brain, the oligodendrocytes.

Although preliminary, this work has implications for minimising the impact of diseases that affect the white matter of the brain, such as multiple sclerosis (MS).

Up until recently it was known that adult stem cells could be made to differentiate into a number of different brain cells -- neurons, astrocytes and other particular brain associated cells -- but not oligodendrocytes.

Director of Neurology and Neurosciences at St Vincent's Hospital in Sydney, Prof Bruce Brew, in collaboration with a group from the University of Sydney and a number of groups in the US, has recently found that adult stem cells can differentiate into oligodendrocytes.

Oligodendrocytes produce the myelin which surrounds neurons and makes electrical conduction along neurons more efficient. People with multiple sclerosis and a number of other white matter diseases produce less myelin which causes poor electrical conduction and therefore poor neurological function. Loss of oligodendrocytes is believed to be one reason for this decrease in myelin production.

The researchers isolated adult stem cells from the bone marrow of humans and mice, injected them into the brains of a mouse model for MS and found that the stem cells migrated and transformed into a number of different brain cells, including oligodendrocytes.

The basic principle on which Brew and colleagues are working is that the adult stem cells will differentiate into appropriate cells according to local or environmental cues. In MS for example, these cues or factors are generated from that part of brain that is diseased, but the timing of the injection is also important for if the factors are not being produced (or if the damage to the brain is not fresh) then transformation of the cells is not as successful.

Brew said he hoped the work would become part of a mutlimodality of therapies for MS in the future. A patient would be stabilised with other drugs first and then their own stem cells isolated from the bone marrow, cultured and given to replace oligodendrocytes and reverse the myelin deficit in their brains.

"It is early days," Brew said. "But this would mean that physical and mental deficits would be minimised. There's no guarantee that deficits will be completely reversed but there is a very good likelihood, in the years to come, that deficits as a result of white matter damage in MS patients will be able to be treated and reversed in part."

The technique itself has wide applicability but specifically it would be useful in the treatment of white matter diseases such as MS and other diseases that have white matter damage as a secondary phenomenon such as infection with encephalitis, meningitis. These infections can be treated effectively with antibiotics and antivirals but patients can be left with a deficit because their white matter has been damaged.

Positive results with triple labelling for oligodendrocyte markers support that the adult stem cells have differentiated and it is not just growth factors coming from other brain cells.

"This is just one piece of the puzzle, we need to keep on confirming with a variety of techniques that these oligodendrocytes are functional and then we need to address the timing of the transplantation," said Brew.

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