Human Cord Blood CD133+ Stem Cells Transplanted to Nod-Scid Mice Provide Conditions for Regeneration of Olfactory Neuroepithelium After Permanent Damage Induced by Dichlobenil

Abstract

The herbicide dichlobenil selectively causes necrosis of the dorsomedial part of olfactory neuroepithelium (NE) with permanent damage to the underlying mucosa, whereas the lateral part of the olfactory region and the nasal respiratory mucosa remain undamaged. We investigated here whether human umbilical cord blood CD133 1 stem cells (HSC) injected intravenously to nod-scid mice pretreated with dichlobenil may engraft the olfactory mucosa and contribute to the regeneration of the damaged NE. We tested HLA-DQa1 DNA and three human microsatellites (Combined DNA Index System) as indicators of engrafted cells, finding polymerase chain reaction evidence of chimaerism in various tissues of the host, including the olfactory mucosa and bulb, at 7 and 31 days following HSC transplantation. Histology, immunohistochemistry, and lectin staining revealed the morphological recovery of the dorsomedial region of the NE in dichlobenil-treated mice that received HSC, contrasting with the lack of regeneration in similarly injured areas as these remained damaged in control nontransplanted mice. FISH analysis, to detect human genomic sequences from different chromosomes, confirmed persistent engraftment of the regenerating olfactory area with chimeric cells. Electro-olfactograms in response to odorants, to test the functionality of the olfactory NE, confirmed the functional damage of the dorsomedial area in dichlobenil-treated mice and the functional recovery of the same area in transplanted mice. These findings support the concept that transplanted HSC migrating to the damaged olfactory area provide conditions facilitating the recovery from olfactory receptor cell loss.

Hematopoietic Stem Cells in Neonates: Any Differences between Very Preterm and Term Neonates?

“…They are considered to possess both hematopoietic and endothelial lineage differentiation potential [35]. The potential use of CD133+ HSPCs in regenerative stem cell therapy is under investigation [36], [37]. Although CD34+/CD133+ HSPCs from preterm cord blood showed higher clonogenic potential, the regenerative potential needs to be evaluated.…”

Calcium‐activated chloride currents in olfactory sensory neurons from mice lacking bestrophin‐2

“…Electro-olfactogram (EOG) recordings were performed as previously described (Franceschini et al 2009). The mouse head was cut sagitally to expose the medial surface of the olfactory turbinates and EOG recordings were measured at the surface of the olfactory epithelium in response to odorant stimuli in the vapour phase.…”

Transplantation of Neural Stem Cells in Anosmic Mice

“…Human cord blood CD133-positive stem cells were intravenously injected to nod-scid mice and this was shown to provide conditions for regeneration of the olfactory neuroepithelium after permanent damage was induced by dichlobenil (16). Adipose tissue-derived stem cells were also intravenously injected to rats after their olfactory nerve was transected (17).…”