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Pain and Inflammation of Chronic Sinusitis, Plus Loss of Smell

Stem Cells “Ability to Switch Their Identity” May Protect, Regenerate

Newswise — In experiments with mice and human tissue samples, Johns Hopkins Medicine researchers report evidence that neuronal stem cells in the part of the nose responsible for the sense of smell transform themselves to perpetuate the long-term inflammation in chronic sinusitis. Results of the study, they say, suggest that the stem cells’ ability to switch their identity to join in the immune response may serve as a protective mechanism, while preserving the potential to regenerate the sense of smell tissue once the inflammation resolves.

In a report, which appears online Sept. 12 in the journal Cell Stem Cell, the scientists say the research also may advance the search for better treatments for the loss of smell that often accompanies chronic sinusitis.

More than just a stuffy nose, chronic sinusitis is marked by ongoing inflammation of the tissue lining the fluid-draining cavities of the skull and nose, resulting in congestion, thick mucus, and facial pain. The condition affects an estimated 30 million–40 million Americans and most lose their sense of smell to some degree. In a percentage, the sense of smell is completely lost, a troubling condition called anosmia. But how sinus inflammation affects the sense of smell has remained unclear.

For many, mucus and tissue swelling blockage alone can’t explain why they lose their smell sense. “Losing this sense is a real disability,” says Andrew Lane, M.D., professor of otolaryngology–head and neck surgery at the Johns Hopkins University School of Medicine. “People can’t detect smells that warn them of impending danger, such as smoke, gas leaks or rotten food. Since most of the perceived flavor of food comes from smell, they lose their ability to taste, affecting their overall enjoyment of life.”

Lane, an otolaryngologist whose practice focuses on treating people with sinus problems, says standard treatments with steroid pills to reduce inflammation don’t always work, and come with side effects, such as bone weakness, change in vision, weight gain and vulnerability to infections. Topical steroids in nasal sprays and rinses can improve sinus congestion and other symptoms, he says, but frequently do not restore the sense of smell.

Neurons in the mucous membrane lining responsible for the sense of smell are called olfactory neurons, and they normally have a remarkable capacity for regeneration, says Lane, even when they are severely damaged by injury. However, in previous studies of a mouse model created by Lane and Johns Hopkins molecular biologist Randall Reed, Ph.D., they found that olfactory neurons damaged by chronic sinus and nasal inflammation fail to regenerate from olfactory stem cells known as horizontal basal cells.

To learn why such basal cells, with stem cell capabilities for regeneration, failed to regenerate olfactory neurons in cases of chronic sinusitis, Lane and postdoctoral fellow Mengfei Chen, Ph.D., studied tissue samples from people with chronic sinusitis and mice bred to develop olfactory inflammation, a model for chronic sinusitis in humans.

They sampled olfactory tissue from the mice early in the experiment, before extensive inflammation set in, and again six to eight weeks later.

The scientists sorted the cells...


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