Activation, Proliferation and Commitment of Endogenous Stem/Progenitor Cells to the Oligodendrocyte Lineage by TS1 in a Rat Model of Dysmyelination

Abstract

Wild-type and myelin-deficient rats received a single intraparenchymal injection of TS1, a specific combination of IGF-1 and transferrin (Tf), into their corpus callosum at postnatal day 4. The fate of endogenous stem cells in the brain was examined by the expression of the stem cell marker nestin, together with Tf, neurofilaments and glial fibrillary acidic protein from 2 to 14 days after injection. Treated mutants lacked nestin expression in the ventricular wall and had an increase in nestin-labeled radial cell processes in the subventricular regions, and extended into the parenchyma. The subventricular zone was populated by healthy new oligodendrocytes (OLs). BrdU incorporation showed that these cells originated by proliferation and were identified as OLs based upon Tf expression. Thus, TS1 is an effective treatment to promote endogenous subventricular zone progenitor proliferation, migration and OL lineage specification. This strategy offers for the first time the possibility of myelin restoration to treat myelin disorders.