Magnetic Targeting of Human Olfactory Mucosa Stem Cells Following Intranasal Administration: a Novel Approach to Parkinson's Disease Treatment.

Among the various therapeutic procedures used for improving PD, stem cell-based therapy has been shown to be a promising method. Olfactory ectomesenchymal stem cells (OE-MSCs) are a great source of stem cells for PD. Also, the intranasal administration (INA) of stem cells to the neural lesion has several advantages over the other approaches to cellular injections. However, improving the efficacy of INA to produce the highest number of cells at the lesion site has always been a controversial issue. For this purpose, this study was designed to apply the magnetically targeted cell delivery (MTCD) approach to OE-MSCs in the injured striatum area through the IN route in order to explore their outcomes in rat models of PD. Animals were randomly classified into four groups including control, PD model, treatment-NTC (treated with INA of non-target cells), and treatment-TC (treated with INA of target cells). The Alg-SPIONs-labeled OE-MSCs were stained successfully using the Prussian blue method with an intracellular iron concentration of 2.73 pg/cell. It was able to reduce signal intensity in the striatum region by increasing the number of these cells, as shown by the magnetic resonance imaging (MRI). Behavioral evaluation revealed that the administration of OE-MSCs with this novel advanced stem cell therapy alleviated Parkinson's motor dysfunction. Further, histological evaluations confirmed the functional enhancement of dopaminergic neuron cells by the expression of Nurr1, Dopamine transporter (DAT), and paired-like homeodomain transcription factor 3 (TH). Overall, this study showed that INA of OE-MSCs in the MTCD approach enhanced stem cells' therapeutic effects in PD models.

Magnetic targeted delivery of the SPIONs-labeled mesenchymal stem cells derived from human Wharton's jelly in Alzheimer's rat models.

Alzheimer's disease (AD) as a progressive neurodegenerative disorder is one of the leading causes of death globally. Among all treatment approaches, mesenchymal stem cells (MSCs)-based therapy is a promising modality for neurological disorders including the AD. This study aimed to magnetically deliver human Wharton's jelly-derived MSCs (WJ-MSCs) toward the hippocampal area within the AD rat's brain and determine the effects of them in cognitive improvement. Rats were randomly divided into five groups as follow: vehicle-treated control, AD model (injection of 8 µg/kg of amyloid ß 1-42), IV-NTC (treated with IV-injected Non-Targeted Cells), IV-TC (treated with IV-injected Targeted Cells), and ICV-NTC (treated with Intracerebroventricular-injected Non-Targeted Cells). WJ-MSCs were labeled with dextran-coated superparamagnetic iron oxide nanoparticles (dex-SPIONs, 50 µg/ml), by bio-mimicry method. SPIONs-labeled MSCs were highly prussian blue positive with an intracellular iron concentration of 2.9 ± 0.08 pg/cell, which were successfully targeted into the hippocampus of AD rats by a halbach magnet array as magnetic targeted cell delivery (MTCD) technique. Presence of SPIONs-labeled cells in hippocampal area was proved by magnetic resonance imaging (MRI) in which signal intensity was reduced by increasing the number of these cells. Behavioral examinations showed that WJ-MSCs caused memory and cognitive improvement. Also, histological assessments showed functional improvement of hippocampal cells by expression of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Overall, this study indicates MTCD approach as an alternative in MSC-based regenerative medicine because it approximately has the same results as invasive directly ICV-injection method has.