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Scientists develop a method to generate efficient stem cells

investigate these processes, often involving expensive, multi-year studies to examine a single aspect of this biology. To address this problem, the Case Western Reserve team developed a rapid and highly efficient method for generating OPCs and oligodendrocytes from pluripotent stem cells from any genetic background—providing new access to these relatively inaccessible brain cells in healthy and diseased states.

In Stem Cell Reports, first author Matthew Elitt, Ph.D., and colleagues leveraged this OPC generation technology to provide new insights and therapeutic strategies for a fatal genetic disorder of myelin, Pelizaeus Merzbacher disease (PMD). The team found that there was an unexpectedly early critical phase in PMD-affected cells characterized by endoplasmic reticulum stress and cell death as OPCs exit their progenitor state. The endoplasmic reticulum is the part of the cell involved in the processing of protein. In PMD, which almost exclusively affects male children, oligodendrocytes are lost and myelin is not properly formed in the brain and spinal cord. Due to their diseased myelin, children with PMD exhibit often-debilitating problems of coordination, motor skills, verbal expression, and learning. Due to the disease's severity, patients typically die before adulthood.

To overcome this early cell death in PMD cells, the team screened thousands of drug-like compounds and found that one, known as Ro 25-6981, was especially successful in rescuing the survival of PMD oligodendrocytes in mouse and human cells in the laboratory and in PMD mice. "Our work is an important first step of a multi-phase process," said Tesar. "We have achieved survival of oligodendrocytes which normally die in the disease. The next step is to figure out how to coax these cells to efficiently myelinate and restore function to patients."

The Case Western Reserve team's findings have implications beyond PMD. Numerous neurological and psychiatric diseases are characterized by myelin loss or dysfunction, including multiple sclerosis, spinal cord injury, and schizophrenia. Measures to regenerate or restore myelin could offer patients hope in these and numerous other disorders affecting the brain and spinal cord.

Source: https://phys.org

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This article was published on Wednesday 10 October, 2018.

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