' '
Deutsch | English    

Forschungsdatenbank PMU-SQQUID

Mesenchymal stem cell conditioning promotes rat oligodendroglial cell maturation.
Jadasz, JJ; Kremer, D; Göttle, P; Tzekova, N; Domke, J; Rivera, FJ; Adjaye, J; Hartung, HP; Aigner, L; Küry, P;
PLoS One. 2013; 8(8):e71814
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig
Rivera Gomez-Barris Francisco J.

Abstract

Oligodendroglial progenitor/precursor cells (OPCs) represent the main cellular source for the generation of new myelinating oligodendrocytes in the adult central nervous system (CNS). In demyelinating diseases such as multiple sclerosis (MS) myelin repair activities based on recruitment, activation and differentiation of resident OPCs can be observed. However, the overall degree of successful remyelination is limited and the existence of an MS-derived anti-oligodendrogenic milieu prevents OPCs from contributing to myelin repair. It is therefore of considerable interest to understand oligodendroglial homeostasis and maturation processes in order to enable the development of remyelination therapies. Mesenchymal stem cells (MSC) have been shown to exert positive immunomodulatory effects, reduce demyelination, increase neuroprotection and to promote adult neural stem cell differentiation towards the oligodendroglial lineage. We here addressed whether MSC secreted factors can boost the OPC"s oligodendrogenic capacity in a myelin non-permissive environment. To this end, we analyzed cellular morphologies, expression and regulation of key factors involved in oligodendroglial fate and maturation of primary rat cells upon incubation with MSC-conditioned medium. This demonstrated that MSC-derived soluble factors promote and accelerate oligodendroglial differentiation, even under astrocytic endorsing conditions. Accelerated maturation resulted in elevated levels of myelin expression, reduced glial fibrillary acidic protein expression and was accompanied by downregulation of prominent inhibitory differentiation factors such as Id2 and Id4. We thus conclude that apart from their suggested application as potential anti-inflammatory and immunomodulatory MS treatment, these cells might also be exploited to support endogenous myelin repair activities.


Useful keywords (using NLM MeSH Indexing)

Animals

Cell Differentiation/drug effects

Culture Media, Conditioned/pharmacology*

Female

Gene Expression Regulation/drug effects

Glial Fibrillary Acidic Protein/genetics

Glial Fibrillary Acidic Protein/metabolism

Hepatocyte Growth Factor/genetics

Hepatocyte Growth Factor/metabolism

Mesenchymal Stromal Cells/metabolism*

Myelin Sheath/genetics

Myelin Sheath/metabolism

Neural Stem Cells/cytology

Neural Stem Cells/drug effects

Neural Stem Cells/metabolism

Oligodendroglia/cytology*

Oligodendroglia/drug effects*

Oligodendroglia/metabolism

Primary Cell Culture

Rats