The breakthrough research at Case Western Reserve School of Medicine now enables "on demand" production of myelinating cells, which provide a vital sheath of insulation that protects neurons and enables the delivery of brain impulses to the rest of the body.
In patients with multiple sclerosis (MS), cerebral palsy (CP), and rare genetic disorders called leukodystrophies, myelinating cells are destroyed and cannot be replaced.
The new technique involves directly converting fibroblasts - an abundant structural cell present in the skin and most organs - into oligodendrocytes, the type of cell responsible for myelinating the neurons of the brain.
"Its 'cellular alchemy,'" said Paul Tesar, assistant professor of genetics and genome sciences at Case Western Reserve School of Medicine and senior author of the study.
"We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy," Tesar said.
In a process termed "cellular reprogramming," researchers manipulated the levels of three naturally occurring proteins to induce fibroblast cells to become precursors to oligodendrocytes (called oligodendrocyte progenitor cells, or OPCs).
Researchers rapidly generated billions of these induced OPCs (called iOPCs).
They showed that iOPCs could regenerate new myelin coatings around nerves after being transplanted to mice - a result that offers hope the technique might be used to treat human myelin disorders.
When oligodendrocytes are damaged or become dysfunctional in myelinating diseases, the insulating myelin coating that normally coats nerves is lost. A cure requires the myelin coating to be regenerated by replacement oligodendrocytes.
Until now, OPCs and oligodendrocytes could only be obtained from fetal tissue or pluripotent stem cells. These techniques have been valuable, but with limitations.
"The myelin repair field has been hampered by an inability to rapidly generate safe and effective sources of functional oligodendrocytes," said co-author and myelin expert Robert Miller.
"The new technique may overcome all of these issues by providing a rapid and streamlined way to directly generate functional myelin producing cells," Miller said.
The study was published in the journal Nature Biotechnology.
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