Neural stem cells: a potential source for remyelination in neuroinflammatory disease.
In multiple sclerosis, the central nervous system is lesioned through invasion of plaque-forming inflammatory cells, primarily contributing to immune attack of myelin and oligodendrocytes. In this report we address the possible activation and differentiation of central nervous system stem cells following such immunological insults in a well-characterized rat model of multiple sclerosis characterised by spinal cord pathology. Dye-labeled central nervous system stem cells, residing within the ependymal layer of the central canal responded to the multiple sclerosis-like conditions by proliferation, while some of the migrating stem cell-derived cells expressed markers typical for oligodendrocytes (04) and astrocytes (glial fibrillary acidic protein, GFAP) in the demyelinated area. Our results indicate that regenerative stem cell activation following immunoactivity is different from that after trauma, exemplified by the slower time course of stem cell proliferation and migration of progeny, in addition to the ability of the stem cell-derived cells to express oligodendrocyte markers. Finally, deleterious effects of macrophages on the stem cell population were evident and may contribute to the depletion of the stem cell population in neuroinflammatory disorders.
Brundin
Lou
L
Neuroimmunology Unit, Centre of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. lou.brundin@ks.se
Brismar
Hjalmar
H
Danilov
Alexandre I
AI
Olsson
Tomas
T
Johansson
Clas B
CB
D000818:Animals; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002232:Carbocyanines / Q000493:pharmacokinetics; D002452:Cell Count; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D053331:Ectodysplasins; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology*; D004805:Ependyma / Q000502:physiology; D005260:Female; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005620:Freund's Adjuvant / Q000633:toxicity; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal / Q000295:instrumentation / Q000379:methods; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000502:physiology*; D018992:Myelin-Associated Glycoprotein / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D019081:O Antigens / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D053331:Ectodysplasins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D008565:Membrane Proteins; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D019081:O Antigens; C430944:O4 antigen, Stenotrophomonas; C007293:DAPI; D005620:Freund's Adjuvant; D001973:Bromodeoxyuridine