Effect of Intranasal Administration of Concentrated Growth Factors on Regeneration of the Olfactory Epithelium in an Olfactory Dysfunction-induced Rat Model

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2024 Feb 28

PMID 38416730

Authors

Naruhiko Kai

Naoya Nishida

Kunihide Aoishi

Taro Takagi

Naohito Hato

Affiliations

Soon will be listed here.

Abstract

Objective: The development of treatments that promote the regenerative capacity of the olfactory epithelium (OE) is desirable. This study aimed to evaluate the effects of intranasal administration of concentrated growth factors (CGFs) in a rat model of olfactory dysfunction.

Study Design: Animal study.

Methods: Nineteen male rats were used. Fourteen olfactory dysfunction models were created by intraperitoneal administration of 3-methylindole. We randomly divided the rats from the olfactory dysfunction model after 1 week into the CGF or saline group; CGFs were administered to seven animals and saline to seven animals. Behavioral assessments using the avoidance test were conducted until day 28 after CGF/saline administration. On day 28, histological evaluation was conducted to determine olfactory epithelial thickness and the olfactory marker protein (OMP)-positive cell count. Five animals were intraperitoneally injected with saline as the control group.

Results: The avoidance rate remained decreased until 28 days after CGF/saline administration, and there was no significant difference between the two groups. Olfactory epithelial thicknesses on day 28 were 38.64 ± 3.17 μm and 32.84 ± 4.50 μm in the CGF and saline groups, respectively. OE thickness was significantly thicker in the CGF group than in the saline group (P = 0.013). The numbers of OMP-positive cells were 40.29 ± 9.77/1.0 × 104 μm2 and 31.00 ± 3.69/1.0 × 104 μm2 in the CGF and saline groups, respectively. The number of OMP+ cells in the CGF group was significantly increased compared with that in the saline group (P = 0.009). Both groups showed no improvement compared with the control group (OE thickness: 54.08 ± 3.36 μm; OMP+ cell count: 56.90 ± 9.91/1.0 × 104 μm2).

Conclusions: The CGF group showed improved olfactory epithelial thickness and OMP-positive cell numbers compared with that in the saline group.

References

Herzog C, Otto T . Administration of transforming growth factor-alpha enhances anatomical and behavioral recovery following olfactory nerve transection. Neuroscience. 2002; 113(3):569-80. DOI: 10.1016/s0306-4522(02)00203-8. View

Lei L, Yu Y, Han J, Shi D, Sun W, Zhang D . Quantification of growth factors in advanced platelet-rich fibrin and concentrated growth factors and their clinical efficacy as adjunctive to the GTR procedure in periodontal intrabony defects. J Periodontol. 2019; 91(4):462-472. DOI: 10.1002/JPER.19-0290. View

Wysocki C, Gilbert A . National Geographic Smell Survey. Effects of age are heterogenous. Ann N Y Acad Sci. 1989; 561:12-28. DOI: 10.1111/j.1749-6632.1989.tb20966.x. View

Dhong H, Chung S, Doty R . Estrogen protects against 3-methylindole-induced olfactory loss. Brain Res. 1999; 824(2):312-5. DOI: 10.1016/s0006-8993(99)01241-x. View

Jafek B, Murrow B, Michaels R, Restrepo D, Linschoten M . Biopsies of human olfactory epithelium. Chem Senses. 2002; 27(7):623-8. DOI: 10.1093/chemse/27.7.623. View

Rodella L, Favero G, Boninsegna R, Buffoli B, Labanca M, Scari G . Growth factors, CD34 positive cells, and fibrin network analysis in concentrated growth factors fraction. Microsc Res Tech. 2011; 74(8):772-7. DOI: 10.1002/jemt.20968. View

Alvarez-Buylla A, Garcia-Verdugo J . Neurogenesis in adult subventricular zone. J Neurosci. 2002; 22(3):629-34. PMC: 6758521. View

Li S, Young T, Huang T . Regeneration of olfactory neuroepithelium in 3-methylindole-induced anosmic rats treated with intranasal chitosan. Biomaterials. 2021; 271:120738. DOI: 10.1016/j.biomaterials.2021.120738. View

Steffens Y, Le Bon S, Lechien J, Prunier L, Rodriguez A, Saussez S . Effectiveness and safety of PRP on persistent olfactory dysfunction related to COVID-19. Eur Arch Otorhinolaryngol. 2022; 279(12):5951-5953. PMC: 9336533. DOI: 10.1007/s00405-022-07560-y. View

10.

Miwa T, Furukawa M, Tsukatani T, Costanzo R, DiNardo L, Reiter E . Impact of olfactory impairment on quality of life and disability. Arch Otolaryngol Head Neck Surg. 2001; 127(5):497-503. DOI: 10.1001/archotol.127.5.497. View

11.

Lee H, Shen E, Shen J, Fu E, Chiu H, Hsia Y . Tensile strength, growth factor content and proliferation activities for two platelet concentrates of platelet-rich fibrin and concentrated growth factor. J Dent Sci. 2020; 15(2):141-146. PMC: 7305442. DOI: 10.1016/j.jds.2020.03.011. View

12.

Masuki H, Okudera T, Watanebe T, Suzuki M, Nishiyama K, Okudera H . Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF). Int J Implant Dent. 2016; 2(1):19. PMC: 5005757. DOI: 10.1186/s40729-016-0052-4. View

13.

Bachler M, Neubuser A . Expression of members of the Fgf family and their receptors during midfacial development. Mech Dev. 2001; 100(2):313-6. DOI: 10.1016/s0925-4773(00)00518-9. View

14.

Noda T, Shiga H, Yamada K, Harita M, Nakamura Y, Ishikura T . Effects of Tokishakuyakusan on Regeneration of Murine Olfactory Neurons In Vivo and In Vitro. Chem Senses. 2019; 44(5):327-338. PMC: 6538963. DOI: 10.1093/chemse/bjz023. View

15.

Tsukatani T, Fillmore H, Hamilton H, Holbrook E, Costanzo R . Matrix metalloproteinase expression in the olfactory epithelium. Neuroreport. 2003; 14(8):1135-40. PMC: 2717620. DOI: 10.1097/00001756-200306110-00007. View

16.

Reden J, Lill K, Zahnert T, Haehner A, Hummel T . Olfactory function in patients with postinfectious and posttraumatic smell disorders before and after treatment with vitamin A: a double-blind, placebo-controlled, randomized clinical trial. Laryngoscope. 2012; 122(9):1906-9. DOI: 10.1002/lary.23405. View

17.

Hummel T, Power Guerra N, Gunder N, Hahner A, Menzel S . Olfactory Function and Olfactory Disorders. Laryngorhinootologie. 2023; 102(S 01):S67-S92. PMC: 10184680. DOI: 10.1055/a-1957-3267. View

18.

Tabata Y, Nagano A, Ikada Y . Biodegradation of hydrogel carrier incorporating fibroblast growth factor. Tissue Eng. 1999; 5(2):127-38. DOI: 10.1089/ten.1999.5.127. View

19.

Yan C, Jang S, Lin H, Ma Y, Khanwalkar A, Thai A . Use of platelet-rich plasma for COVID-19-related olfactory loss: a randomized controlled trial. Int Forum Allergy Rhinol. 2022; 13(6):989-997. PMC: 9877663. DOI: 10.1002/alr.23116. View

20.

Jafek B, Linschoten M, Murrow B . Anosmia after intranasal zinc gluconate use. Am J Rhinol. 2004; 18(3):137-41. View