From Transcriptome to Behavior: Intranasal Injection of Late Passage Human Olfactory Stem Cells Displays Potential in a Rat Model of Parkinson’s Disease

Parkinson’s disease (PD) is
one of the most common neurodegenerative
disorders, which is caused by the loss of dopaminergic (DAergic) neurons.
Thus, cell replacement therapy (CRT) might be regarded as an alternative
therapy to effectively treat motor functional defects in PD patients.
Human olfactory ectomesenchymal stem cells (OE-MSCs) are a novel type
of mesenchymal stem cells (MSCs) with a strong tendency to differentiate
into DAergic neurons. However, there are various barriers to successful
CRT including the proliferation capacity of stem cells at higher passage
numbers as well as the route of stem cell delivery. In this regard,
we aimed to explore the efficacy of late passage OE-MSC administration
through the intranasal (IN) route in PD rat models. Herein, the proliferation
capacity of OE-MSCs was compared at early and late passage numbers;
then, the results were validated via RNA sequencing analysis. Subsequently,
the efficacy of IN injection of late passage OE-MSC in PD models was
evaluated. The results manifested the absence of noticeable differences
in proliferation capacity and signaling pathways in OE-MSCs at early
and late passage numbers. Moreover, it was found that the IN administration
of OE-MSCs with a high passage number substantially increased the
levels of DAergic markers and improved the motor function in rat models
of PD. Overall, our findings suggested that OE-MSCs with a high passage
number are a promising CRT candidate due to their fundamental potential
to provide a large number of cells with an enormous proliferation
capacity. Moreover, they exhibit the high efficiency of IN administration
as a noninvasive route of late-passage OE-MSC delivery for CRT, particularly
for PD.