Investigating Intranasal Olfactory Mucosa Progenitor Cells Administration in Compensating Hippocampal Atrophy in Alzheimer Disease: A Novel Perspective

Abstract

Based on a trial conducted to assess the homing capacity of human OPMCs applied intranasally, the OPMCs migrated to the sites of soma atrophy and axonal swelling. Mapping the position of the applied cells, the mean distance (+SD) from OMPCs to regions of axonal damage indicated B-APP⁺ (the same marker in CA1 hippocampal atrophy in AD) was 71.8+60.3 µm; OMPCs to atrophic cell bodies indicated p-c-jun⁺ (the same marker in CA2 hippocampal atrophy in AD) was 188.7 + 320 µm; OMPCs to random sites was 3929.3 + 2636.3 µm. Another trial was conducted on mice to confirm whether the OMPCs also exhibit high capacity of neurogenesis. The presence of relay neurons derived from the OMPCs differentiation was evident and traced by the Wheat germ agglutinin (WGA) expression in the injured regions in the spinal cords of the subjects. Based on the analysis of evidence and reviewing the literature related to the pathogenesis and markers of AD hippocampal atrophy, human OMPCs intranasal administration have high homing capacity which make them have a strong potential to safely migrate to the site of axonal damage (B-APP⁺ region) and sites of soma atrophy (p-c-jun⁺ region) in hippocampus of AD patients. At the site of homing, OMPCs differentiate into trans-synaptic relay neurons, expressing WGA protein, which reconstructs the neural pathways in the site of atrophy not only by acting as a scaffold, but also by differentiating into relay-neurons CONCLUSION: OMPCs intranasal administration is a novel technique which may have potential to restore neural pathways in subjects with AD presenting with hippocampal atrophy.