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Rejuvenated brain stem cells may hold key to remyelination

New research, published in the journal Nature, demonstrates that it is possible to restore older brain stem cells to a younger, healthier state – something that may help them to remyelinate.

A multi-disciplinary research team, based at the Wellcome-MRC Cambridge Stem Cell Institute (University of Cambridge), studied young and old rat brains and in particular the impact of age-related “brain stiffening” on the function of oligodendrocyte progenitor cells (OPCs). These are brain cells which make myelin and are damaged in MS. Their function also declines with age in healthy people.

To determine whether the loss of function in aged OPCs was reversible, the researchers transplanted older OPCs from older rats into the soft, spongy brains of younger animals. They found the older brain cells were rejuvenated, and began to behave like the younger, more vigorous cells.

To study this further, the researchers developed new materials in the lab with varying degrees of stiffness and used these to grow and study the rat brain stem cells in a controlled environment. The materials were engineered to have a similar softness to either young or old brains.

To fully understand how brain softness or stiffness influences cell behaviour, the researchers investigated Piezo1 - a protein found on the cell surface, which tells the cell whether the surrounding environment is soft or stiff.

Dr Kevin Chalut, who co-led the research, said: "We were fascinated to see that when we grew young, functioning rat brain stem cells on the stiff material, the cells became dysfunctional and lost their ability to regenerate, and began to function like aged cells. What was especially interesting, however, was that when the old brain cells were grown on the soft material, they began to function like young cells - in other words, they were rejuvenated."

"When we removed Piezo1 from the surface of aged brain stem cells, we were able to trick the cells into perceiving a soft surrounding environment, even when they were growing on the stiff material," explained Professor Robin Franklin, who co-led the research with Dr Chalut. "What's more, we were able to delete Piezo1 in the OPCs within the aged rat brains, which lead to the cells becoming rejuvenated and once again able to assume their normal regenerative function."

Source: MS-UK 23/08/2019

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