Monday, 11 June 2012

Research: Experimental Remyelination

Jagielska A, Norman AL, Whyte G, Van Vliet KJ, Guck J, Franklin RJ. Mechanical environment modulates biological properties of oligodendrocyte progenitor cells. Stem Cells Dev. 2012 May 30. [Epub ahead of print]

Myelination and its regenerative counterpart of remyelination represent one of the most complex cell-cell interactions in the central nervous system (CNS). The biochemical regulation of neuronal axon myelination via the proliferation, migration, and differentiation of oligodendrocyte progenitor cells (OPCs) has been characterized extensively. However, most biochemical analysis has been conducted in vitro on OPCs adhered to substrata of stiffness that is orders of magnitude greater than that of the in vivo CNS environment. Little is known of how variation in such mechanical properties over the physiological range affects OPC biology.

Here we show that OPCs are mechanosensitive. Cell survival, proliferation, migration, and differentiation capacity in vitro depend on the mechanical stiffness of polymer hydrogel substrata. Most of these properties are optimal at the intermediate values of CNS tissue stiffness. Moreover, many of these properties measured for cells on gels of optimal stiffness differed significantly from those measured on glass or polystyrene. The dependence of OPC differentiation on the mechanical properties of the extracellular environment provides motivation to revisit results obtained on non-physiological, rigid surfaces. We also find that OPCs stiffen upon differentiation but that they do not change their compliance in response to substratum stiffness, which is similar to embryonic stem cells but different from adult stem cells. These results form the basis for further investigations into the mechanobiology of cell function in the CNS and may specifically shed new light on the failure of remyelination in chronic demyelinating diseases such as multiple sclerosis.

In cell culture myelin forming cells are often grown on the plastic of the flasks that contain the cells in tissue culture. This plastic is very stiff and harder than the type of thing (substrate) that myelin-forming cells would encounter in the brain. This study in tissue culture suggests that the stiffness/flexibility of the the substrate on which myelin forming cells grow can influence how they divide and mature. Thus the substrate, that is the environment that the immature myelin forming cell encounters in the MS lesion will determine whether it can repair or not. Throught study of how these different substrates influnece myelination we may be able to modify the envrinoment within the MS brain to make it more condusive to repair. For example you know plants can't grow on glass and are not so great when grown on sand but give them soil and off they go.

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