Induction of human mesenchymal stem cells into dopamine-producing cells with different differentiation protocols.
Several reports have shown that human mesenchymal stem cells (MSCs) are capable of differentiating outside the mesenchymal lineage. We sought to induce MSCs to differentiate into dopamine-producing cells for potential use in autologous transplantation in patients with Parkinson's disease (PD). Following cell culture with various combinations of differentiation agents under serum-free defined conditions, different levels of up-regulation were observed in the protein expression of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Further analysis of selected differentiation protocols revealed that the induced cells displayed a neuron-like morphology and expressed markers suggesting neuronal differentiation. In addition, there was an increase in Nurr 1, the dopaminergic transcription factor gene, concomitant with a decrease gamma-aminobutyric acid (GABA)ergic marker expression, suggesting a specific dopaminergic direction. Moreover, the induced cells secreted dopamine in response to depolarization. These results demonstrate the great therapeutic potential of human MSCs in PD.
Laboratory of Neurosciences, Felsenstein Medical Research Center, Petah Tiqwa, 49100 Israel.
Ran
R
Barzilay
Inna
I
Kan
Tali
T
Ben-Zur
Shlomo
S
Bulvik
Eldad
E
Melamed
Daniel
D
Offen
D000328:Adult; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D004298:Dopamine / Q000096:biosynthesis*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008875:Middle Aged; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010641:Phenotype; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine