Transplantation of CG4 oligodendrocyte progenitor cells in the myelin-deficient rat brain results in myelination of axons and enhanced oligodendroglial markers

Abstract

Transplantation of oligodendrocyte (Ol) progenitor cells into the central nervous system is a promisingapproach for the treatment of myelin disorders. This approach requires providing adequate numbers of healthy cells with myelinating potential. We recently showed the successful transplantation of Ol progenitors into the myelin-deficient (md) rat brain. In the present work, CG4 cells, a cell line with properties of Ol progenitors, were labeled with fast blue and grafted into P3-P5 pups born to carrier mothers. Examination of host brains 2 weeks posttransplant indicated that CG4 cells display a much more extensive migration capacity than their wild-type counterparts. These cells synthesized myelin components. In addition, ultrastructural analysis showed myelin formation along axons of md hosts in various brain regions, including corpus callosum, cerebellum, and brainstem. Furthermore, in situ hybridization studies performed on sagittal sections revealed extensive expression of transferrin-mRNA within the md host parenchyma. The high survival and functional features displayed by CG4 cells after transplantation, together with their striking wide distribution within the host parenchyma, as assessed by the presence of myelinated fibers in mutant hosts, emphasizes the importance of using highly motile and proliferative Ol progenitor cells. Strategies to improve the condition and life span of md rat pups are currently under investigation.

Conditional Tet-Regulated Over-Expression of Hoxa2 in CG4 Cells Increases Their Proliferation and Delays Their Differentiation into Oligodendrocyte-like Cells Expressing Myelin Basic Protein

“…Furthermore, a poly-Llysine substrate or the presence of pleitrophin in the GM (Rumsby et al 1999) promotes undifferentiated bipolar CG4 cells to disperse, migrate, and begin morphological differentiation. Importantly, when transplanted in vivo the undifferentiated bipolar CG4 cells can migrate to areas of damage and remyelinate axons (Espinosa de los Monteros et al 1997;Franklin et al 1995;Franklin et al 1996;Tontsch et al 1994;Tourbah et al 1997). Thus, the ex vivo strategy described in the present study for genetically modifying CG4 cells offers the additional possibility of studying the effects of over-or under-expression of a gene of interest, such as the Hoxa2 gene, in vivo.…”

Stage-specific Expression of Myelin Basic Protein in Oligodendrocytes Involves Nkx2.2-mediated Repression That Is Relieved by the Sp1 Transcription Factor

“…Upon withdrawal of growth factors, these cells are capable of differentiating into mature oligodendrocytes. After being transplanted into the central nervous system, they function as oligodendrocytes in vivo to myelinate axons (22). Nkx2.2 is expressed in oligodendrocyte precursor cells and is important for oligodendrocyte specification in the developing spinal cord.…”

Stem Cells: An Answer to Treat Neurodegeneration?

“…Current approaches for the treatment of MS include monoclonal antibodies, chimeric molecules and hematopoietic cells. CG4 oligodendrocyte progenitor cells are showing hope for the treatment of MS [21]. Much research has been carried out to understand the role of ESCs in the treatment of MS.…”