Induction of human mesenchymal stem cells into dopamine-producing cells with different differentiation protocols

Ran Barzilay, Inna Kan, Tali Ben-Zur, Shlomo Bulvik, Eldad Melamed, Daniel Offen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 γ-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.

Original languageEnglish
Pages (from-to)547-554
Number of pages8
JournalStem Cells and Development
Volume17
Issue number3
DOIs
StatePublished - 1 Jun 2008

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