Wnt/β-catenin Signaling Pathway Enhances Early Dopaminergic Differentiation of Trabecular Meshwork Derived Mesenchymal Stem Cells.

Background: Parkinson’s disease is the second most common neurodegenerative disorder. Degeneration of dopaminergic neu-rons in the Substantia nigra causes the loss of dopamine related functions. So far Wnt/β-catenin signaling pathway is shown to be involved in differentiation of dopaminergic neurons. Our preliminary results in the present study showed that the neural crest-derived trabecular meshwork MSC (TM-MSC) could be an appropriate source to differentiate into neurons. Therefore, we sought to examine neural differentiation potential of these cells compared to the two other sources of MSCs including adipose-derived (ADMSCs) and bone marrow (BMSCs) mes-enchymal stem cells and to determine the role of Wnt/β-catenin signaling pathway in early dopaminergic differentiation.Materials and Methods: To address these questions, the cells were cultured in the presence and absence of neural induction medium for six days and analyzed by real time PCR and im-munofluorescence staining. To examine the effect of Wnt/β-catenin signaling on dopaminergic differentiation, CHIR (Wnt agonist; 3 µM) and IWP-2 (Wnt antagonist, 3 µM) were used. Results: Our morphological analysis showed that TM-MSCs exhibited a better neural characteristic than ADMSCs and BM-SCs. Also, more enhanced expression of Nurr-1, the early dopa-minergic marker, was present in TM-MSCs compared to ADM-SCs and BMSCs. In the neurally induced TM-MSCs, there were significant increased expression of Nurr-1 and MAP2 compared to those in the non-induced control cells. A combined treatment with CHIR and the neural induction medium, further enhanced the expression of Nurr-1 and MAP2 as well as those of the Wnt/β-catenin signaling target genes, c-Myc and Cyclin D1. Conversely, a combined treatment with IWP2 and the neu-ral induction medium significantly decreased the expression of Wnt/β-catenin target genes and the neural markers.Conclusion: Altogether, we suggest that TM-MSCs have a higher neural potency than other commonly used MSCs and can potentially be induced towards the dopaminergic differen-tiation via the activation of Wnt/β-catenin pathway.

Keywords:

Wnt/β-catenin , Dopaminergic , Trabecular Meshwork