Neuropathol Appl Neurobiol. 2010 Sep 15. doi: 10.1111/j.1365-2990.2010.01124.x. [Epub ahead of print]
Brain and spinal cord affected by amyotrophic lateral sclerosis induce differential growth factors expression in rat mesenchymal and neural stem cells.
Nicaise C, Mitrecic D, Pochet R.
Laboratory of Histology, Neuroanatomy and Neuropathology, Université Libre de Bruxelles, Brussels,
Belgium Laboratory for Neurogenetics and Developmental Genetics, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia.
Stem cell research raises hopes for incurable neurodegenerative diseases. In amyotrophic lateral sclerosis (ALS), affecting the motoneurons of the central nervous system (CNS), stem cell-based therapy aims to replace dying host motoneurons 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. Aim: 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 (Ngf) and brain derived neurotrophic factor (Bdnf) were significantly upregulated in both NSC and MSC cultures upon stimulation with SOD1(G93A) CNS extracts. Fibroblast growth factor 2 (Fgf2), insulin-like growth factor (Igf1) and glial derived neurotrophic factor (Gdnf) were upregulated in NSC, while the same factors were downregulated in MSC. Vascular endothelial growth factor A (Vegfa) upregulation was restricted to MSC and fibroblasts. Surprisingly, SOD1(G93A) spinal cord, but not the brain extract, upregulated Bdnf in MSC and Gdnf 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.
© 2010 Radboud University Nijmegen Medical Centre.
PMID: 20846186 [PubMed – as supplied by publisher]