IL-16 expression is upregulated during in vitro demyelination and inhibits OPC differentiation and myelination.

Institute researchers have examined the potential of human mesenchymal stromal cells (MSC) to ameliorate disease in a mouse model of Multiple Sclerosis (known as experimental autoimmune encephalomyelitis or EAE). 

In this paper, published in Acta Neuropathologica Communications, they compared classical human MSC purified from bone marrow (hBM-MSCs) to a novel MSC isolated from human olfactory mucosal tissue (hOM-MSCs).

The olfactory system, which comprises nervous tissue and is associated with the sense of smell, is known to regenerate throughout life, something unique to CNS tissue.

This work shows that, although both MSC types can ameliorate disease if delivered during the initial onset of symptomatic disease, only hOM-MSCs improved disease outcome if administered during established disease when animals had severe neurological deficits.

At early time points post-hOM-MSC treatment, animals had reduced levels of circulating IL-16, which was reflected in both the ability of immune cells to secrete IL-16 and the level of IL-16 in spinal cord inflammatory lesions. Further in vitro investigation revealed an inhibitory role for IL-16 on oligodendrocyte differentiation and myelination.

Combined, the data suggests that human hOM-MSCs may have therapeutic benefit in the treatment of MS via an IL-16-mediated pathway, especially if administered during active demyelination and inflammation.

Professor Sue Barnett said: "Previously, we have shown that a population of cells can be isolated from human nasal tissue. These cells, termed hOM-MSCs, promote repair of damaged brain and spinal cord cells grown in Petri dishes and promote recovery in an animal model of spinal cord injury.

"In this paper, we show that treatment with hOM-MSCs reduces clinical symptoms in a mouse model of multiple sclerosis. These experiments provide additional data to support the translation of hOM-MSCs into the clinic."


Human olfactory mesenchymal stromal cell transplantation ameliorates EAE revealing an inhibitory role for IL16 on myelination

  • Susan L. LindsayAleksandra M. MolędaLindsay M. MacLellan, Siew Min Keh, Daniel E. McElroyChristopher LiningtonCarl S. Goodyear & Susan C. Barnett
  • Published: 29 January 2022. Acta Neuropathologica Communications. 10(1):12.

Image Legend: Figure 6. IL-16 expression is upregulated during in vitro demyelination and inhibits OPC differentiation and myelination.(f) Immunohistochemical images of control CNS myelinating cultures or after IL-16 (100 ng/ml) treatment from Day 12. Axons are stained with SMI-31 (shown in red) and myelin stained with PLP (shown in green). Quantification revealed that IL-16 treatment from day 12, significantly reduced the number of myelinated axons compared to control cultures (n = 3, all conditions)

First published: 3 March 2022