May 12, 2016
MS Society-funded team devises a new technique to study the movement of myelin-forming cells
As the central nervous system (CNS) develops, oligodendrocyte progenitor cells (OPCs) spread throughout the brain and spinal cord. Over time, they develop into mature oligodendrocytes, the cells responsible for producing myelin – the insular coating that surrounds nerve fibers and allows information to be transmitted efficiently throughout the brain. OPCs also lie at the heart of myelin repair; in cases when myelin undergoes damage, OPCs journey into areas of damage and mature into oligodendrocytes capable of generating new myelin.
In MS, for reasons that are still under study the remyelination process breaks down – the brain accumulates myelin damage and MS-related symptoms worsen. Scientists believe that this remyelination failure is caused, in part, by the limited ability of OPCs to penetrate MS lesions. Recent evidence suggests that this inability to infiltrate damaged areas is caused by certain molecules produced in the lesion. Precisely what these molecules are, and what role they play in OPC migration, is an area of great interest to MS researchers.
Led by Dr. Rashmi Kothary, scientists from the Ottawa Hospital Research Institute have studied OPC movement through different molecular environments. The team explored how certain molecules, present in both the brain as well as MS lesions, interact with a protein called integrin-linked kinase (ILK) found just under the outermost membrane of OPCs. They aimed to better understand how this interaction influenced OPC migration, with the view to identify a new target for remyelinating therapies. These findings were published in the journal BMC Neuroscience.
The authors developed a cell culture technique that allowed them to study how OPCs moved through different molecular environments. They began by harvesting OPCs from genetically modified mice. The genetic alteration made it possible for the researchers to easily remove the ILK gene and its associated protein. ILK-depleted and ILK-rich OPCs were then transferred to specially treated culture dishes coated with one of two molecules: laminin-2 or fibronectin. Both molecules are found throughout the brain as well as in MS lesions and are believed to facilitate OPC movement.
OPCs were allowed to migrate within the culture dishes over a period of 24 hours, with distances travelled recorded at the 4, 10 and 24-hour marks. The technique allowed Dr. Kothary’s team to compare how OPCs, with or without ILK, travelled through environments rich in either laminin-2 or fibronectin.
When grown on fibronectin, ILK-depleted OPCs were unable to travel as far as ILK-rich cells. The effect was most remarkable after 10 and 24 hours. When grown on laminin-2, ILK-depleted OPCs initially slowed down at the 4 hour mark, but by 10 hours, showed similar migration to ILK-rich cells.
Dr. Kothary and his team have developed a novel technique to study the movement of genetically altered OPCs through different molecular environments. Their system will make it easier for scientists to answer important questions concerning how OPCs interact with a variety of molecules found in and around MS lesions.
The team also demonstrated how the interaction between ILK and either laminin-2 or fibronectin encouraged OPC migration; specifically, they showed that laminin-2 kickstarts the OPC’s journey while fibronectin maintains its momentum in the cellular environment. As the authors note, by describing the mechanisms governing OPC movement, researchers can better design therapeutics that encourage myelin-producing cells to penetrate and remyelinate lesions and improve the lives of people living with MS.
O’Meara R et al. (2016). A new in vitro mouse oligodendrocyte precursor cell migration assay reveals a role for integrin-linked kinase in cell motility. BMC Neuroscience. 17:7.