Induction of glial glutamate transporters in adult mesenchymal stem cells.
Adult bone marrow mesenchymal stem cells are multipotent cells that can differentiate into a variety of mesodermal tissues. Recent studies have reported on their ability to also evolve into non-mesodermal cells, especially neural cells. While most of these studies revealed that manipulating these cells triggers the expression of typical neurone markers, less is known about the induction of neuronal- or glial-related physiological properties. The present study focused on the characterisation of glutamate transporters expression and activity in rat mesenchymal stem cells grown in culture conditions favouring their differentiation into astroglial cells. Ten days exposure of the cells to the culture supplement G5 was found to increase the expression of nestin (neuro-epithelial stem cell intermediate filament), an intermediate filament protein expressed by neural stem cells. Simultaneously, a robust induction of the high-affinity glutamate transporter GLT-1 (and GLAST) expression was detected by RT-PCR and immunocytochemistry. This expression was correlated with a highly significant increase in the Na+-dependent [3H]D-aspartate uptake. Finally, while glial fibrillary acidic protein immunoreactivity could not be detected, the induced expression of the astrocytic enzyme glutamine synthetase was demonstrated. These results indicate that in vitro differentiation of adult mesenchymal stem cells in neural precursors coincides with the induction of functional glutamate transport systems. Although the astrocytic nature of these cells remains to be confirmed, this observation gives support to the study of mesenchymal stem cells as a promising tool for the treatment of neurological diseases involving glutamate excitoxicity.
de Hemptinne
Isabelle
I
Laboratoire de Pharmacologie Expérimentale, Université catholique de Louvain, Brussels, Belgium.
Vermeiren
Céline
C
Maloteaux
Jean-Marie
JM
Hermans
Emmanuel
E
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000493:pharmacokinetics; D015152:Blotting, Northern / Q000379:methods; D001853:Bone Marrow; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology; D013194:Staining and Labeling / Q000379:methods; D018800:Thy-1 Antigens / Q000378:metabolism; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology; D014316:Tritium / Q000493:pharmacokinetics
D027322:Amino Acid Transport System X-AG; D020934:Ciliary Neurotrophic Factor; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D027342:Excitatory Amino Acid Transporter 2; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D012333:RNA, Messenger; D009418:S100 Proteins; D018800:Thy-1 Antigens; D014316:Tritium; D016222:Fibroblast Growth Factor 2; D001224:Aspartic Acid; D014212:Tretinoin; D012964:Sodium; D005974:Glutamate-Ammonia Ligase