Effect of intranasally-administered adipose derived stem cells on age-related changes of rat olfactory bulb: A histological and immunohistochemical study

Abstract

Introduction: Age-related olfactory decline is increasingly recognized to be a major health problem with no known treatment yet, reflecting on individual safety, nutrition, physical and mental well-being. Intranasal administration of adipose derived stem cells (ADSCs) could be an ideal curative strategy, bypassing the blood brain barrier with no risk for systemic exposure.Aim: To evaluate the age related structural changes in the olfactory bulb (OB) of rats and to assess the possible therapeutic role of intranasally-administered ADSCs after different time points.Materials and Methods: Thirty aged female rats, of two years old, in addition to five adult rats, six months old were used in this study. They were divided into group I; served as adult control group, group II; served as aged non-treated group, and group III that served as aged group treated with 1×106 of PKH26-labelled intranasal ADSCs. Rats of groups I and II were sacrificed after 14 days of the beginning of the experiment. Rats of group III were sacrificed after two hours, one, three, and 15 days respectively, five rats/time point. Dissection of OB was done at each time point, and processed for light microscopic examination after staining with H&E, toluidine blue, and immunohistochemically-staining for synaptophysin and S-100B. Morphometric study and statistical analysis were also done.Results: Aged rats showed structural degenerative changes in all layers of the OB. Intranasal administration of ADSCs reached the OB as early as two hours after administration, and managed to gradually reverse its age-induced structural damage.Conclusion: Intranasal administration of ADSCs managed to reverse the OB structure to the adult appearance. Hence, it is recommended to include the intranasal ADSCs as a powerful therapeutic strategy for olfactory bulb dysfunction in aged individuals.