Comparing neuroprotective effects of CDNF-expressing bone marrow derived mesenchymal stem cells via differing routes of administration utilizing an in vivo model of Parkinson’s disease

The potential value of cerebral dopamine neurotrophic factor (CDNF) in treating Parkinson’s disease (PD) remains controversial. To evaluate the therapeutic effects of CDNF-expressing bone marrow derived mesenchymal stem cell (CDNF-MSCs) injections in a rat model of Parkinson’s disease, we chose three different routes of CDNF-MSC administration, including intra-striatal, intra-ventricular, and intravenous pathways. Parkinsonism was induced by intra-striatal unilateral injection of 6-OHDA and then rats were subsequently randomized into three groups for either intra-striatal, intra-ventricular or intravenous injection for CDNF-MSC grafting. Therapeutic effects were evaluated by observing dopaminergic (DA) neurons both in the substantia nigra compacta (SNc) and within the striatum and by monitoring apomorphine-induced rotational behavior (circling). Data show that one intra-venous administration of CDNF-MSCs was ineffective for treating Parkinson’s disease-like neurodegeneration. Conversely, intra-striatal grafts can reduce loss of DA neurons both in the SNc and striatum with improvement of Parkinson’s-related behaviors, compared to intra-ventricular injections. Thus, intra-striatal grafts composed of CDNF-MSCs may provide a strategy for therapeutic delivery to treat PD.