Finding an inflammation off-switch may lead to stem cell therapies for multiple sclerosis

ImitolaLabImageRTFSomeday, stem cells could serve as therapies for multiple sclerosis (MS) and other life-changing neurological diseases. Already they are helping researchers better understand the disease. Using stem cells in the laboratory, researchers are studying how inflammatory processes in the brain strip protective myelin from around neurons, gradually damaging those cells and shrinking brain tissue. Researchers hope to use stem cells to develop new drug treatments for MS, especially targeting the progression of disability and neurodegeneration that affects a great majority of patients with MS, says Jaime Imitola, MD, director of the Progressive Multiple Sclerosis Mutidisciplinary Clinic and Translational Research Program at The Ohio State University Wexner Medical Center.

"I am particularly interested in how the inflammation within MS affects neuronal and oligodendrocyte progenitor cells. These stem cells within the brain have tremendous plasticity and have the potential to repair damage caused by the disease. However, this plasticity is impaired during the chronic disease," Dr. Imitola explains. "If we understand the inflammatory mechanisms that target the tremendous molecular plasticity of stem cells leading to damage in the brain, then we can generate new medications that target these processes."

Using data from human stem cells, Dr. Imitola and his colleagues are looking for genes that could control repair in the central nervous system. "After we find candidate genes, we use mouse and human cells to study the function of these genes to see whether they are involved in either the differentiation of oligodendrocytes or in the generation of new neurons," Dr. Imitola says.

"Our goal is reverse engineer the MS disease progression at the cellular and molecular level in the lab, using cells derived from patients. This is a very complex and arduous task," Dr. Imitola says.

Using mouse-derived stem cells, he and his colleagues are growing tiny chunks of neocortex, known as cerebral organoids, in the laboratory. With these tissues, they can test the effect of shutting down or increasing the expression of particular candidate genes, providing a more direct way to test mechanisms of neuronal repair during inflammation.

"Our ultimate goal is to offer solutions to so many of our patients, who plead for answers. When I see them in our MS center, I feel their suffering, frustration and hope. It is empowering to us to keep working – persevering – to get to the finish line and improve their lives," Dr. Imitola shares.

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