Abstract
Background aims
Cell replacement therapy is considered a promising alternative in the treatment of
degenerative diseases, and in this context, mesenchymal stromal cells (MSCs) have
been proposed for transplantation in Parkinson disease (PD). Thus far, the results
of animal studies are found to be inconsistent and inconclusive regarding the therapeutic
ability of the cells. This study investigated the efficacy of fetal liver (FL)-MSC-derived
dopaminergic (DA) neuronal primed cells for correction of parkinsonian symptoms in
mice.
Methods
FL-MSCs were differentiated for 21 days in the presence of a combination of neurotropic
factors. The extent of cellular reprogramming was analyzed by quantitative polymerase
chain reaction for DA-specific neuronal gene expressions and protein expressions by
immuno-cytochemistry. The functionality of the cells was determined by electrophysiology
and dopamine release assays. Ten-day-primed neuron-like cells or unprimed MSCs were
transplanted into the 6-hydroxydopamine (6-OHDA)-lesioned striatum using a stereotaxic
device. Dopamine-secreting properties and behavioral studies were used to assess improvement
of parkinsonian symptoms.
Results
The differentiated cells expressed DA-specific genes and proteins, while exhibiting
a high level of voltage-gated potassium current. Furthermore, neuronal primed cells
differentiated into tyrosine hydroxylase immunoreactive and dopamine-secreting functional
neuron-like cells. Symptomatic correction of PD in the recipient mice within 2 months
of transplantation was also observed.
Discussion
FL-MSC-derived primed neuron-like cells integrated into the striatum of PD mice, improving
parkinsonian symptoms. This study demonstrates an effective cell-based therapy for
PD.
Key Words
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© 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
