Intranasal Delivery of MSCs Shown to Improve PD Symptoms in Rats
Three percent of applied MSCs were proliferative 4.5 months after application.!--h2>
An international team of researchers say that delivery of mesenchymal stem cells (MSCs) through the nose to the brains of rats with Parkinson disease yielded improvement in motor function and reversed the dopamine deficiency characteristic of the disease. They note that intranasal delivery of MSCs avoids the tissue trauma, related inflammation, and brain swelling associated with surgical implantation of therapeutic stem cells. The researchers also believe that this noninvasive method would also make it possible to provide repeat stem cell treatments over time.
The findings appear in Rejuvenation Research, and the paper is titled “Therapeutic Efficacy of Intranasally Delivered Mesenchymal Stem Cells in a Rat Model of Parkinson Disease.”
In the study the investigators demonstrated intranasal delivery of MSCs to the brains of unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats. This resulted in the appearance of cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord.
Out of 1x106 MSCs applied intranasally, 24% survived for at least 4.5 months in the brains of the 6-OHDA rats as assessed by quantification of enhanced green fluorescent protein (EGFP) DNA. Quantification of proliferating cell nuclear antigen-positive EGFP-MSCs showed that 3% of applied MSCs were proliferative 4.5 months after application.
Intranasal application of MSCs increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra and completely eliminated the 6-OHDA-induced increase in terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine, 5’-triphosphate-biotin nick end labeling staining of these areas.
Intranasal application of EGFP-labeled MSCs prevented any decrease in the dopamine level in the lesioned hemisphere. The lesioned side of the control animals, however, revealed significantly lower levels of dopamine 4.5 months after 6-OHDA treatment.
Behavioral analyses revealed improvement of motor function of the Parkinsonian forepaw to up to 68% of the normal value 40–110 days after intranasal delivery of 1x106 MSCs. The cells decreased the concentrations of inflammatory cytokines interleukin-1b (IL-1b), IL-2, -6, -12, tumor necrosis factor, interferon-g, and granulocyte-macrophage colony-stimulating factor in the lesioned side to their levels in the intact hemisphere.