Dopaminergic Induction of Umbilical Cord Mesenchymal Stem Cells by Conditioned Medium of Choroid Plexus Epithelial Cells Reduces Apomorphine-Induced Rotation in Parkinsonian Rats.

Abstract

Degeneration of dopaminergic neurons in Parkinson's disease (PD) implies cell replacement using potentially differentiable sources as a promising therapeutic solution. We tested the capacity of conditioned medium from choroid plexus epithelial cells (CPECs-CM) to induce the dopaminergic potential of umbilical cord matrix mesenchymal stem cells (UCMSCs). We isolated UCMSCs from human umbilical cord and CPECs from rat brain. Following expansion and characterization, CPECs-CM were collected, tested for expression of various growth factors, and applied to UCMSCs. Differentiation was examined and UCMSCs were injected into 6-OHDA-leasioned striatum to test their survival and function. RT-PCR and immuno-staining demonstrated neuronal/dopaminergic signaling in UCMSCs induced by CPECs-CM and accelerated by addition of retinoic acid (RA) and fibroblast growth factor-2. Expression of β-tubulin-3, Nestin and MAP2 confirmed neuronal differentiation whereas tyrosine hydroxylase, aromatic acid decarboxylase and dopamine transporter were expressed as signs of dopaminergic differentiation. Post-transplantation, the UCMSCs survived, showed reduced rate of apoptosis and led to animals' recovery from apomorphine-induced rotations. The combination of neurotrophic factors present in CPECs-CM and RA can synergize to maximize dopaminergic differentiation of potential cell sources including UCMSCs. Our study may have implications for PD cell replacement therapy.