Intrastriatal transplantation of mouse bone marrow-derived stem cells improves motor behavior in a mouse model of Parkinson's disease.
Strategies of cell therapy for the treatment of Parkinson's disease (PD) are focused on replacing damaged neurons with cells to restore or improve function that is impaired due to cell population damage. In our studies, we used mesenchymal stromal cells (MSCs) from mouse bone marrow. Following our novel neuronal differentiation method, we found that the basic cellular phenotype changed to cells with neural morphology that express specific markers including those characteristic for dopaminergic neurons, such as tyrosine hydroxylase (TH). Intrastriatal transplantation of the differentiated MSCs in 6-hydroxydopamine-lesioned mice led to marked reduction in the amphetamine-induced rotations. Immunohistological analysis of the mice brains four months post transplantation, demonstrated that most of the transplanted cells survived in the striatum and expressed TH. Some of the TH positive cells migrated toward the substantia nigra. In conclusion, transplantation of bone marrow derived stem cells differentiated to dopaminergic-like cells, successfully improved behavior in an animal model of PD suggesting an accessible source of cells that may be used for autotransplantation in patient with PD.
Offen
D
D
Laboratory of Neurosciences, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. doffen@post.tau.ac.il
Barhum
Y
Y
Levy
Y S
YS
Burshtein
A
A
Panet
H
H
Cherlow
T
T
Melamed
E
E
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D004298:Dopamine / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine