Mesenchymal Stem Cells Prime Proliferating Adult Neural Progenitors Toward an Oligodendrocyte Fate

Abstract

Oligodendrogenesis encompasses lineage specification of neural progenitor cells (NPCs) and differentiation into oligodendrocytes that ultimately culminates in the myelination of central nervous system axons. Each individual process must be tightly regulated by extracellular and cell-intrinsic mechanisms, whose identities are barely understood. We had previously demonstrated that soluble factors derived from rat mesenchymal stem cells (MSCs) induce oligodendrogenesis in differentiating adult NPCs under differentiation conditions. However, since lineage specification predominantly occurs in proliferating progenitors and not necessarily during early differentiation, we investigated if soluble factors derived from MSCs are able to prime NPCs to the oligodendroglial fate already under proliferation conditions. Therefore, we analyzed the effects of a 3 weeks stimulation of adult NPCs under proliferation conditions with conditioned media derived from MSCs (MSC-CM) in terms of cell morphology, proliferation, cell-specific marker expression profile, response to growth factor withdrawal (GFW), cell-lineage restriction, and expression of glial fate determinants. While MSC-CM did not affect the proliferation rate of NPCs, it boosted the formation of 2¢, 3¢-cyclic-nucleotide-3¢-phosphodieesterase (CNPase)-and myelin basic protein-expressing oligodendrocytes after GFW, even when cells were exposed to an astrogenic milieu. Moreover, it reinforced the proper development of oligodendrocytes, since it ensured a sustained expression of the functional marker CNPase. Finally, the presence of MSC-CM reduced the anti-oligodendrogenic determinant Id2 in proliferating NPCs, thus increasing the relative proportion of the pro-oligodendrogenic factor Olig2 expression. In summary, MSCs prime proliferating progenitors and, thus, reinforce cell fate choice and accelerate differentiation toward the oligodendrocyte lineage. The present findings underscore the potential use of MSCs in cell therapies for remyelination such as in multiple sclerosis and spinal cord injury. Moreover, they urge the identification of the oligodendrogenic activity(ies) derived from MSCs to develop novel molecular therapies for demyelinating diseases.

Mesenchymal Stem Cell Conditioning Promotes Rat Oligodendroglial Cell Maturation

“…Furthermore, we received from the ethics committee of the animal research facility of the Heinrich-Heine-University permits to kill animals and to preserve tissues (O69/2011; O118/11). Ethical considerations and details on the generation of primary oligodendroglial cells as well as of mesenchymal stem cells have previously been reported by us [10], [14]–[16].…”

The effects of adipose tissue-derived mesenchymal stem cell transplantation during the acute and subacute phases following spinal cord injury

“…MSCs have been shown to modulate many of the detrimental effects associated with acute damage in SCI by neuronal protection and inflammation suppression, as well as the secretion of multiple factors that modulate neuronal growth, and the reduction of cavity formation (26,27).…”

Third Ventricular Glioblastoma Multiforme: Case Report and Literature Review

“…22 Neural stem cells from the subventricular zone migrate during injury to produce oligodendrocytes in the fimbriae fornix. 25 In this fashion, the mass may have originated in the progenitor neural cells of the fornix and spread into both the septum pellucidum and the third ventricle, which could be explained clinically by the patient's impaired memory. 11 …”