Cerebral organoids shed light on cells that generate the myelin cells that protect the axons of neuron. In multiple sclerosis, inflammatory processes attack the myelin of neurons in the brain and spinal cord.
The exact cause of multiple sclerosis (MS) is unknown, but it is believed that both environmental and genetic factors play a role in the pathogenesis of the disease. Symptoms are precipitated by brain and spinal cord inflammation resulting in damage to the protective myelin sheath that surrounds of axons of neurons.
Genetic factors are thought to play a role in the risk of developing MS and the course of disease progression, but their role is not fully understood. To gain more insight into the effects of genetic factors on MS, Nicolas Daviaud, Ph.D., and other researchers from the Tisch Multiple Sclerosis Research Center of New York developed a novel human cell model of MS. The research was published earlier this month in Biology Open.
The researchers collected blood cells from healthy participants and from people with primary progressive MS (PPMS), secondary progressive MS (SPMS), and relapsing remitting MS (RRMS). They then reprogrammed the cells into induced pluripotent stem cells (iPSCs), which are lab-grown stem cells able to differentiate into other types of cells. The iPSCs were used to derive cerebral organoids (or “mini-brains”) that retained the donor’s genetic information but did not contain blood vessels or immune cells. Thus, the inflammatory process associated with MS was absent. The organoids contained both neurons and glial cells.
After six weeks of growth, the researchers found that the organoids derived from cells of people with MS, particularly those with PPMS, showed a decrease in oligodendrocyte differentiation. These are glial cells heavily involved in myelin production. Daviaud and colleagues linked the disruption in oligodendrocyte growth with decreased levels of p21 protein, which helps regulate cell growth and division.
The researchers see the p21 protein as a potential target for future MS therapies. They anticipate using their cerebral organoid models as a tool for understanding the influence of genetic factors in MS development.
“With our novel mini-brain models, we’re taking a critical step toward understanding how a patient’s genetic background influences MS pathogenesis – and to ultimately discovering the origin of MS. We look forward to applying this novel technology to upcoming research and one day, toward a long-awaited cure for MS patients,” Saud A. Sadiq, M.D., director and chief research scientist at the Tisch MS Research Center of New York and study author, said at a press conference.