title: Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model.
abstract: Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain's white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrow-derived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinated mouse brain. As a result, oligodendrocyte progenitors were recruited surrounding the graft due to the expression of various trophic signals by the grafted MSCs. Although there was no significant reaction in the non-grafted side, in the grafted regions oligodendrocyte progenitors were detected. These progenitors were derived from the nearby tissue as well as from the neurogenic niches, including the subependymal zone and dentate gyrus. Once near the graft site, the cells matured to myelinating oligodendrocytes. Finally, electrophysiological studies demonstrated that axonal conduction velocity was significantly increased in the grafted side of the fimbria. In conclusion, we demonstrate here that in chronic demyelinated white matter, BM-MSC transplantation activates oligodendrocyte progenitors and induces remyelination in the tissue surrounding the stem cell graft.
authors.affiliation: Neuroscience Institute, University Miguel Hernandez-Spanish Council for Scientific Research (UMH-CSIC), Alicante, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Jaramillo-Merchán
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: J L
authors.initials: JL
authors.lastname: Ivorra
authors.forename: D
authors.initials: D
authors.lastname: Pastor
authors.forename: M C
authors.initials: MC
authors.lastname: Viso-León
authors.forename: J A
authors.initials: JA
authors.lastname: Armengól
authors.forename: M D
authors.initials: MD
authors.lastname: Moltó
authors.forename: E
authors.initials: E
authors.lastname: Geijo-Barrientos
authors.forename: S
authors.initials: S
authors.lastname: Martínez
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D002908:Chronic Disease; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018891:Dentate Gyrus / Q000473:pathology; D004195:Disease Models, Animal; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009186:Myelin Sheath / Q000378:metabolism*; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism; D009431:Neural Conduction; D055495:Neurogenesis; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D055153:Stem Cell Niche
chemical_list: D009414:Nerve Growth Factors; D003471:Cuprizone