Effects of murine and human bone marrow-derived mesenchymal stem cells on cuprizone induced demyelination.
For the treatment of patients with multiple sclerosis there are no regenerative approaches to enhance remyelination. Mesenchymal stem cells (MSC) have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE), an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS). In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes.
Department of Neurology, Hannover Medical School, Hannover, Germany.
Jasmin
J
Nessler
Karelle
K
Bénardais
Viktoria
V
Gudi
Andrea
A
Hoffmann
Laura
L
Salinas Tejedor
Stefanie
S
Janßen
Chittappen Kandiyil
CK
Prajeeth
Wolfgang
W
Baumgärtner
Annemieke
A
Kavelaars
Cobi J
CJ
Heijnen
Cindy
C
van Velthoven
Florian
F
Hansmann
Thomas
T
Skripuletz
Martin
M
Stangel
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002452:Cell Count; D058948:Cell Tracking; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology; D003471:Cuprizone; D019610:Cytoprotection; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D005247:Feeding Behavior; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D039441:Integrin alpha4 / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D009930:Organic Chemicals / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D018925:Chemokines; D009930:Organic Chemicals; C070080:PKH 26; D012333:RNA, Messenger; D039441:Integrin alpha4; D003471:Cuprizone; D017228:Hepatocyte Growth Factor