Stem cells transplantation supports the repair of injured olfactory neuroepithelium after permanent lesion.

We investigated whether human cord blood-selected CD133+ stem cells (HSC) may engraft the olfactory mucosa and contribute to restoration of neurolfactory epithelium (NE) in nod-scid mice damaged by dichlobenil. The herbicide dichlobenil selectively causes necrosis of the dorsomedial part of the NE and underlying mucosa, while the lateral part of the olfactory region remains undamaged. The aim of this research was to demonstrate that HSC stimulate self-renewal of neuronal stem cells and promote their differentiation into bipolar olfactory neurons to replace the injured NE. By PCR, we tested the presence of 3 human specific microsatellites (CODIS), used as DNA markers for traceability of the engrafted cells, demonstrating their presence in various tissues of the host, including the olfactory mucosa, after one month from transplantation. By immunohistochemistry and lectin staining, we demonstated that, in injured mice, HSC contributed to stimulating residual endogenous olfactory neurons, promoting recovery of the original phenotype of the NE, in contrast to the lack of spontaneous regeneration in similar injured areas always seen in the non-transplanted control mice. Multiple color-FISH (M-FISH) analysis detecting 7 human genomic sequences present in different chromosomes provided further evidence of positive prolonged engraftment of chimeric cells in the olfactory mucosa. This study provides the first evidence that transplanted HSC migrating to the neurolfactory mucosa may contribute to NE structure restoration with resumption of the sensorineural olfactory loss.