Brain and spinal cord affected by amyotrophic lateral sclerosis induce differential growth factors expression in rat mesenchymal and neural stem cells.
Stem cell research raises hopes for incurable neurodegenerative diseases. In amyotrophic lateral sclerosis (ALS), affecting the motoneurones of the central nervous system (CNS), stem cell-based therapy aims to replace dying host motoneurones by transplantation of cells in disease-affected regions. Moreover, transplanted stem cells can serve as a source of trophic factors providing neuroprotection, slowing down neuronal degeneration and disease progression.


OBJECTIVE
To determine the profile of seven trophic factors expressed by mesenchymal stem cells (MSC) and neural stem cells (NSC) upon stimulation with CNS protein extracts from SOD1-linked ALS rat model.


METHODS
Culture of rat MSC, NSC and fibroblasts were incubated with brain and spinal cord extracts from SOD1(G93A) transgenic rats and mRNA expression of seven growth factors was measured by quantitative PCR.


RESULTS
MSC, NSC and fibroblasts exhibited different expression patterns. Nerve growth factor and brain-derived neurotropic factor were significantly upregulated in both NSC and MSC cultures upon stimulation with SOD1(G93A) CNS extracts. Fibroblast growth factor 2, insulin-like growth factor and glial-derived neurotropic factor were upregulated in NSC, while the same factors were downregulated in MSC. Vascular endothelial growth factor A upregulation was restricted to MSC and fibroblasts. Surprisingly, SOD1(G93A) spinal cord, but not the brain extract, upregulated brain-derived neurotropic factor in MSC and glial-derived neurotropic factor in NSC.


CONCLUSIONS
These results suggest that inherent characteristics of different stem cell populations define their healing potential and raise the concept of ALS environment in stem cell transplantation.
Nicaise
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Laboratory of Histology, Neuroanatomy and Neuropathology, Université Libre de, Bruxelles, Brussels, Belgium. cnicaise@ulb.ac.be
Mitrecic
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D
Pochet
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D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics
D036341:Intercellular Signaling Peptides and Proteins; D013482:Superoxide Dismutase