Regenerative effect of neural-induced human mesenchymal stromal cells in rat models of Parkinson's disease.
BACKGROUND
Human bone marrow multipotent mesenchymal stromal cells (hMSC), because of their capacity of multipotency, may provide an unlimited cell source for cell replacement therapy. The purpose of this study was to assess the developmental potential of hMSC to replace the midbrain dopamine neurons selectively lost in Parkinson's disease.


METHODS
Cells were isolated and characterized, then induced to differentiate toward the neural lineage. In vitro analysis of neural differentiation was achieved using various methods to evaluate the expression of neural and dopaminergic genes and proteins. Neural-induced cells were then transplanted into the striata of hemi-Parkinsonian rats; animals were tested for rotational behavior and, after killing, immunohistochemistry was performed.


RESULTS
Following differentiation, cells displayed neuronal morphology and were found to express neural genes and proteins. Furthermore, some of the cells exhibited gene and protein profiles typical of dopaminergic precursors. Finally, transplantation of neural-induced cells into the striatum of hemi-Parkinsonian rats resulted in improvement of their behavioral deficits, as determined by apomorphine-induced rotational behavior. The transplanted induced cells proved to be of superior benefit compared with the transplantation of naive hMSC. Immunohistochemical analysis of grafted brains revealed that abundant induced cells survived the grafts and some displayed dopaminergic traits.


CONCLUSIONS
Our results demonstrate that induced neural hMSC may serve as a new cell source for the treatment of neurodegenerative diseases and have potential for broad application. These results encourage further developments of the possible use of hMSC in the treatment of Parkinson's disease.
Laboratory of Neurosciences, Felsenstein Medical Research Center and Department of Neurology, Rabin Medical Center, Beilinson Campus Tel Aviv University, Sackler School of Medicine, Petah-Tikva, Israel.
Y S
YS
Levy
M
M
Bahat-Stroomza
R
R
Barzilay
A
A
Burshtein
S
S
Bulvik
Y
Y
Barhum
H
H
Panet
E
E
Melamed
D
D
Offen
D000328:Adult; D000368:Aged; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D008875:Middle Aged; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*
D003470:Culture Media; D004298:Dopamine