Reprogramming Fibroblasts into Oligodendrocyte Progenitor Cells May Lead to Cure for Multiple Sclerosis and Cerebral Palsy

Working with mouse tissues, investigators have developed a method for converting skin or lung fibroblasts into fully functional oligodendrocytes, the type of cell responsible for myelinating the neurons of the brain and which are lost in myelin disorders such as multiple sclerosis and cerebral palsy.

Cell-based therapies for myelin disorders require technologies to generate functional oligodendrocyte progenitor cells (OPCs). In this regard, investigators at Case Western Reserve School of Medicine (Cleveland, OH, USA) described the direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either three or eight defined transcription factors.

They reported in the April 14, 2013, online edition of the journal Nature Biotechnology that the iOPCs exhibited a bipolar morphology and global gene expression profile consistent with bona fide OPCs. They could be expanded in vitro for at least five passages while retaining the ability to differentiate into multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs were capable of ensheathing host axons and generating compact myelin.

“The myelin repair field has been hampered by an inability to rapidly generate safe and effective sources of functional oligodendrocytes,” said contributing author Dr. Robert Miller, professor of neurosciences at the Case Western Reserve School of Medicine. “The new technique may overcome all of these issues by providing a rapid and streamlined way to directly generate functional myelin producing cells.”

“It is cellular alchemy,” explained senior author Dr. Paul Tesar, assistant professor of genetics and genome sciences at Case Western Reserve School of Medicine. “We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy.”

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