Is-32: Transcription Factor-Mediated Reprogramming of Fibroblasts to Expandable, Myelinogenic Oligodendrocyte Progenitor Cells

Tesar P *,


Remyelination remains an elusive goal for treating disorders such as multiple sclerosis and leukodystrophies. A number of recent studies have laid the foundation and catalyzed current enthusiasm for the use of line age conversion as a potential regenerative therapy for many neurological disorders. However, transplantation and functional integration of fully mature cells such as neurons and oligodendrocytes has clear limitations, therefore expandable somatic progenitors are a sought after target for cell-based therapies. We show the ability to directly convert mouse embryonic and lung fibroblasts to ‘induced’ oligodendrocyte progenitor cells (iOPCs) using a defined set of transcription factors. The iOPCs exhibit morphological and molecular features consistent with bona fide OPCs and can be expanded in vitro for multiple passages while retaining the ability to differentiate into ‘induced’ oligodendrocytes (iOLs) capable of ensheathing and myelinating axons both in vitro and in vivo. Our data demonstrate that the lineage conversion of somatic cells to expandable iOPCs may provide a novel strategy to study the molecular control of oligodendrocyte lineage identity and potentially for autologous remyelinating therapies in the future.