Effects of Systemic Transplantation of Adipose Tissue-Derived Stem Cells on Olfactory Epithelium Regeneration

Objective/Hypothesis: The purpose of the study was to investigate the effect of intravenous adipose tissue-derived stem cell (ADSC) transplantation on olfactory epithelium regeneration following transection of the olfactory nerve in rats. Study Design: This was a experimental study using primary cultures of mesenchymal stem cells derived from animal adipose tissue with histological analysis of animal olfactory tissue. Methods: All rats underwent unilateral transection of the olfactory nerve to induce degeneration of olfactory epithelium, and then were observed for regeneration according to time sequences. ADSCs were cultivated from neck adipose tissue of rats, and systemically injected into the experimental group. The control group was injected with phosphate buffered solution, instead of ADSCs. After 30 days, regeneration of olfactory epithelium was observed with olfactory marker protein (OMP) and proliferating cell nuclear antigen. To observe the characteristics of the transplanted ADSCs, olfactory epithelium was stained with von Willebrant factor and OMP. Results: After olfactory nerve transection, mature olfactory cells disappeared in 5 days, but gradually regained their thickness with increased cell numbers at approximately 10 to 15 days. By 30 days post-transection, the thickness and cellular composition of epithelium was almost restored to baseline levels pretransection. However, OMP expressions remained decreased compared with day 0 or 3. Systemically injected ADSCs were transplanted into the olfactory epithelium and survived beyond 4 weeks. The ADSCs promoted regeneration of olfactory epithelium in the animal model and differentiated into olfactory receptor neurons and endothelial cells. Conclusions: Our findings suggest the feasibility of ADSC transplantation as a treatment for head trauma-related olfactory dysfunction.