The effect of rat bone marrow derived mesenchymal stem cell transplantation for restoration of olfactory dysfunction

Abstract

Purpose: Stem cells are the cell with infinite proliferation and function of pluripotency. Stem cell can be divided into embryonic stem cell or adult stem cell based on acquisition process of cell and differentiation potential. Among these, adult stem cell has been used for cell therapy with the function of differentiating into tissue specific functional cells after isolating from fully developed organs. Major examples are hematopoietic stem cell and mesenchymal stem cell. The marrow derived mesenchymal stem cells are cell that can differentiate to cartilage cell, skeleton cell, and neuron cell. The mesenchymal stem cells are known to secrete various neurotophic factors in degenerative nervous systematical environment controlling nerve regeneration through differentiation into neuron or fusion. Neurotophic factors are an essential factor for growth, regeneration, differentiation of nerve in nervous system. The development process of vertebrates which take part of growth and directional of axon and neurodendrite, secretion of neuron delivery substance, creation and plasticity of new synapse in adult nervous system regulated by neurotrophic factors. Undifferentiated mesenchymal stem cell has neuron growth factor such as neurotophic factor, nerve growth factor (NGF) and brain derived neurotrophic factor (BNDF). The purpose of the study is to investigate the correlation between regeneration of olfactory function for NGF and BDNF in BMSCs transplantation. Method:In order to make anosmia animal mode,l using seven-weeks old Sprague-Dawley. Olfactory mucosa of Rat were damaged with Triton X-100 then PBS and Fibroblast, BMSCs directly injected from medial canthus to rear of nasal cavity group was compared with normal (no treatment) group. The olfactory mucosa damage by Triton X-100, after three days maximize, PBS, Fibroblast, BMSCs were injected after three days Triton X-100 treatment. The behavioral test was performed after 3days, 1, 2, 4 weeks to verify the recovery of olfactory function on time variation. In addition, thickness was checked by H&E staining to verify the morphological recovery and regeneration of olfactory epithelium, and revelation of olfactory marker protein (OMP) was analyzed using IHC staining. The OMP expression was increased in IHC staining, thickness recovery in olfactory epithelium by H&E staining, and behavioral test were measured for functional improvement, mRNA expression was measure quantitatively to find correlation of neurotrophic factor NGF, BDNF, and expression rate, and qualitative analysis was performed using IHC staining.Conclusion: When BMSCs were transplanted, the expression of neurotrophic factor NGF and BDNF was increased, olfaction improvement was judged by recovering of olfactory dysfunction with increase in the expression of OMP. The study showed a correlation between regeneration of olfactory function for NGF and BDNF in BMSCs transplantation and increase in the OMP expression level.