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

Mol Neurobiol. 2021 Aug;58(8):3835-3847. doi: 10.1007/s12035-021-02392-z. Epub 2021 Apr 15.

Abstract

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.

Keywords: Intranasal administration; Magnetic targeting; Olfactory mucosa stem cells; Parkinson’s disease; Superparamagnetic iron oxide nanoparticle.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Cells, Cultured
  • Combined Modality Therapy
  • Humans
  • Magnetite Nanoparticles / administration & dosage*
  • Male
  • Olfactory Mucosa / drug effects
  • Olfactory Mucosa / metabolism*
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / therapy*
  • Rats
  • Rats, Wistar
  • Stem Cell Transplantation / methods*
  • Treatment Outcome

Substances

  • Magnetite Nanoparticles