Adult neurotrophic factor-secreting stem cells: a potential novel therapy for neurodegenerative diseases.
BACKGROUND
Stem cell-based therapy is a promising approach for the treatment of neurodegenerative disease. In our laboratory, a novel protocol has been developed to induce bone marrow-derived mesenchymal stem cells into neurotrophic factor-secreting cells. These cells produce and secrete factors such as BDNF (brain-derived neurotrophic factor) and GDNF (glial-derived neurotrophic factor).


OBJECTIVE
To evaluate the migratory capacity and efficacy of NTF-SC in animal models of Parkinson's disease and Huntington's disease.


METHODS
MSCs underwent two-phase medium-based induction. An efficacy study was conducted on the 6-hydroxydopamine-induced lesion, a rat model for Parkinson's disease. Cells were transplanted on the day of 6-OHDA administration, and amphetamine-induced rotations were measured as a primary behavioral index. In a second experiment, migratory behavior was examined by transplanting cells a distance from a quinolinic acid-induced striatal lesion, a rat model for Huntington's disease. Migration, in vivo, was monitored using longitudinal magnetic resonance imaging scans followed by histology.


RESULTS
NTF-SCs attenuated amphetamine-induced rotations by 45%. HPLC analysis demonstrated a marked decrease in dopamine depletion, post-cellular treatment. Moreover, histological assessments revealed that the engrafted cells migrated and acted to regenerate the damaged striatal dopaminergic nerve terminal network. In a preliminary work on an animal model for Huntington's disease, we demonstrated by high resolution MR images and correlating histology that induced cells migrated along the internal capsule towards the QA-induced lesion.


CONCLUSIONS
The induced MSCs are a potential therapy for neurodegenerative diseases, due both to their NTF secretion and their ability to migrate towards the diseased tissue.
Sadan
Ofer
O
Laboratory of Neurosciences, Felsenstein Medical Research Center and Department of Neurology, Rabin Medical Center (Beilinson Campus), Petah Tikva, Israel.
Shemesh
Noam
N
Cohen
Yoram
Y
Melamed
Eldad
E
Offen
Daniel
D
D053687:Adult Stem Cells / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006816:Huntington Disease / Q000175:diagnosis / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D010300:Parkinson Disease / Q000175:diagnosis / Q000628:therapy*; D051381:Rats
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor