Shedding light on misbehaving cells

Much like a kindergarten full of unruly toddlers, the cells that contribute to the body’s crucial processes can’t always be trusted to do what you want or expect them to do. Now IBEC researchers have made an important breakthrough that could contribute to the development of therapies for spinal and neural diseases:  they’ve figured out exactly what it is that makes certain cells misbehave in particular circumstances.

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Some parts of the human body are renewed throughout life. If we could harness their regenerative mechanisms or properties and apply them to the parts that don’t, we’d make huge steps towards achieving new therapies for many injuries and diseases. The olfactory system is one such area that can renew itself, and it does this by using olfactory ensheathing cells (OECs) to guide newly formed axons – long, slender projections of nerve cells – towards the body’s central nervous system.

As a result, OECs have already been transplanted to see if this ability also works to promote axonal regeneration in spinal cord injuries and neural diseases; but in this environment, researchers have come across a hurdle. OECs need to move or migrate homogeneously and cohesively in order to be able to perform their task of guiding the axons, but factors in the spine area affect their behaviour so that they move individually or in the wrong direction.

Now, in a study published this week in the journal Cellular and Molecular Life Sciences, IBEC researchers demonstrate that particular proteins are responsible for blocking the correct migration of OECs in the spine, therefore stopping them from performing the important task of guiding the young axons. If these proteins can be inhibited, the OECs could perform in the ‘correct’ way, as they do in the olfactory system, and aid axonal growth.

“We took rodent OECs, and used cell tracking and traction force microscopy to analyze OEC migration and its mechanical properties over myelin, an insulating material around axons in the brain and central nervous system,” explains José Antonio del Río, a group leader at IBEC. “The results show that these cells express all the components of what’s called the Nogo receptor complex, a combination of receptors used by myelin to inhibit the movement of the OECs, and that inhibiting Nogo with a protein called NEP1-40 enhances their migratory capacity again.”

These results, which stem from an interdisciplinary effort involving the expertise of Prof. del Rio’s Molecular and Cellular Neurobiotechnology group, the cell migration know-how of IBEC’s Integrative Cell and Tissue Dynamics team, and technologies lent by the institute’s Nanobioengineering group, offer insights into how research into OECs as a potential therapy in spine and neural pathologies could be developed. “It suggests that a cell-based strategy to overcome the inhibitory action of myelin is needed to enhance migration and, thus, axon regrowth,” says Dr. del Río.

Nocentini S, Reginensi D, Garcia S, Carulla P, Moreno-Flores MT, Wandosell F, Trepat X, Bribian A, Del Río JA. (2011). Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single-cell tracking and traction force microscopy. Cell Mol Life Sci, in press