title: Time-dependent fate of transplanted neural precursor cells in experimental autoimmune encephalomyelitis mice.
abstract: Transplanted Neural Precursor Cells (NPCs) are capable of long-distance migration inside the inflamed CNS, but exhibit limited myelinating capacities in animal models of Multiple Sclerosis (MS). Inflammation seems to be both beneficial for the recruitment and migration of NPCs and restrictive for their terminal differentiation. In the present study, a set of transplantation experiments was applied in order to investigate the migratory potential, the differentiation pattern and long-term survival of NPCs in Experimental Autoimmune Encephalomyelitis (EAE) mice, the animal model of MS. The in vitro differentiation potential of NPCs in the presence of either pro- (TNFa, INFγ) or anti- (TGFb) inflammatory cytokines was also analyzed. According to the in vivo results obtained, at the acute phase of EAE only a small fraction of transplanted NPCs succeed to differentiate, whereas at chronic phase most of them followed a differentiation process to glial cell lineage along white matter tracts. However, this differentiation was not fully completed, since 8 months after their transplantation a number of NPCs remained as pre-oligodendrocytes. Glial differentiation of NPCs was also found to be inhibited or promoted following their treatment with TNFa or TGFb respectively, in vitro. Our findings suggest that inflammation triggers migration whereas the anti-inflammatory component is a prerequisite for NPCs to follow glial differentiation thereby providing myelinating oligodendrocytes. It is speculated that the fine balance between the pro- and anti-inflammatory determinants in the CNS may be a key factor for transplanted NPCs to exhibit a better therapeutic effect in EAE and MS. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation."
authors.affiliation: Second Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Macedonia, Greece.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Giannakopoulou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grigoriadis
authors.forename: Eleni
authors.initials: E
authors.lastname: Polyzoidou
authors.forename: Athanasios
authors.initials: A
authors.lastname: Lourbopoulos
authors.forename: Eleni
authors.initials: E
authors.lastname: Michaloudi
authors.forename: Georgios C
authors.initials: GC
authors.lastname: Papadopoulos
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000601:surgery*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins / Q000009:adverse effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000009:adverse effects; D011509:Proteoglycans / Q000378:metabolism; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D049452:Green Fluorescent Proteins; D007381:Intermediate Filament Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D064231:Nestin; D010446:Peptide Fragments; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C577485:Nes protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55)