Improvement of spatial learning and memory deficits by intranasal administration of human olfactory ecto-mesenchymal stem cells in an Alzheimer's disease rat model.

Mesenchymal stem cells therapy provides a new perspective of therapeutic approaches in the treatment of neurodegenerative diseases. The present study aimed to investigate the effects of intranasally transplanted human "olfactory ecto-mesenchymal stem cells" (OE-MSCs) in Alzheimer's disease (AD) rats. In this study, we isolated OE-MSCs from human olfactory lamina propria and phenotypically characterized them using immunocytochemistry and flow cytometry. The undifferentiated OE-MSCs were transplanted either by intranasal (IN) or intrahippocampal (IH) injection to rat models of AD, which were induced by injecting amyloid-beta (Aß) intrahippocampally. Behavioral, histological, and molecular assessments were performed after a three-month recovery period. Based on the results, intranasal administration of OE-MSCs significantly reduced Aß accumulation and neuronal loss, improved learning and memory impairments, and increased levels of BDNF (brain-derived neurotrophic factor) and NMDAR (N-methyl-D-Aspartate receptors) in the AD rat model. These changes were more significant in animals who received OE-MSCs by intranasal injection. The results of this study suggest that OE-MSCs have the potential to enhance cognitive function in AD, possibly mediated by BDNF and the NMDA receptors.

Intranasal delivery of sunitinib: A new therapeutic approach for targeting angiogenesis of glioblastoma.

Glioblastoma multiforme (GBM) is one of the most vascular among solid tumors, and despite the use of multimodal therapies, the survival of these patients is poor. In order to target angiogenesis in GBM as a promising strategy, an antiangiogenic drug is required. This study was designed to evaluate the effects of sunitinib, a multityrosine kinase inhibitor with tumor proliferation and angiogenesis inhibitory properties, on GBM-bearing rats. Given the ineffective drug delivery to the brain due to the presence of the blood-brain barrier (BBB), intra-nasal (IN) drug delivery has recently been considered as a non-invasive method to bypass BBB. Therefore, in the current study, IN was used as an ideal method for the delivery of sunitinib to the brain, and the effects of this method were also compared to the OR administration of the sunitinib. GBM was induced in the brain of male Wistar rats, and they were randomly divided into 4 groups; IN-STB (sunitinib intranasal delivery), IN-sham (placebo intranasal delivery), OR-STB (sunitinib oral delivery) and OR-sham (placebo oral delivery). After the end of the treatment period, an MRI of animals' brains showed a reduction in tumor growth in the treatment groups. Immunohistochemistry revealed that sunitinib inhibits angiogenesis in GBM in both OR and IN delivery methods. Analysis of liver tissue and enzymes showed that IN delivery of sunitinib had less hepatotoxicity than the OR method. Overall, it was found that IN sunitinib delivery could be used as a potential non-hepatotoxic alternative for the treatment of GBM.

Olfactory mucosa stem cells delivery via nasal route: a simple way for the treatment of Parkinson disease.

Finding a simple and effective way for transferring cells to the brain lesion site with minimum side effects mounts a challenge in cell therapy. Cell delivery via nasal route using the bypassing the blood-brain barrier (BBB) property is a simple and non-invasive strategy without serious complications such as trauma. Therefore, it is a suitable technique to treat neurodegenerative disorders like Parkinson's disease (PD). Olfactory ectomesenchymal stem cells (OE-MSCs) located in the lamina propria of olfactory mucosa could be differentiated into dopaminergic neurons under in vitro and in vivo conditions. Thus, OE-MSCs represent a good source of Parkinson's stem cell-based therapy. In this research, we studied thirty male rats (n = 10 in each group) in three control (Ctl), lesion (LE), and intranasal administration (INA) groups to investigate the therapeutic effect of intranasal injection of OE-MSCs in the Parkinson's animal models. To do so, we examined the homing variation of OE-MSCs in different brain regions such as olfactory bulb (OB), cortex, striatum (Str), hippocampus (HPC), and substantia nigra (SN). The results of real-time PCR and immunohistochemistry (IHC) analysis showed the expression of dopaminergic neuron markers such as PITX3, PAX2, PAX5 (as dopaminergic neurons markers), tyrosine hydroxylase (TH), and dopamine transporter (DAT) 2 months after INA of 1 × 106 OE-MSCs. The results confirmed that IN OE-MSCs delivery into the central nervous system (CNS) was powerful enough to improve the behavioral functions in the animal models of PD.