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鼻内神经干细胞移植对嗅觉缺失诱导小鼠模型嗅觉上皮再生的影响。

Effects of intranasal neural stem cells transplantation on olfactory epithelium regeneration in an anosmia-induced mouse model.

作者信息

Hazir Burak, Ceylan Alper, Bagariack Emin Ümit, Dayanir Duygu, Araz Milat, Ceylan Banu Tijen, Oruklu Nihan, Sahin Muammer Melih

机构信息

Department of Otorhinolaryngology/Head and Neck Surgery, Ankara City Hospital, Ankara, Turkey.

Faculty of Medicine, Department of Otorhinolaryngology/Head and Neck Surgery, Gazi University, Ankara, Turkey.

出版信息

Sci Rep. 2025 May 16;15(1):17015. doi: 10.1038/s41598-025-01358-8.

Abstract

This study aims to investigate the efficacy of intranasally transplanted neural stem cells (NSCs) in anosmia-induced mice. Twenty-four male mice were included in the study. A food-finding test (FFT) was performed beforehand to confirm that all mice had normal olfactory functions. The mice were then randomly divided into two groups (Groups 1 and 2) and anosmia was induced by 3-methylindole (3-MI). In the first week following the 3-MI injection (week 1), mice in Group 1 received intranasal saline, while mice in Group 2 received intranasal NSCs. The NSCs were prepared from green fluorescent protein (GFP)-transgenic mice. Olfactory function was evaluated through weekly FFTs. One week after NSC or saline administration (week 2), half of the mice in each group were randomly selected and sacrificed for histological examination. The remaining mice were sacrificed for histological examination in week 4. At week 4, the olfactory epithelium of all mice was also examined by polymerase chain reaction (PCR) to detect GFP + cells. The NSC group showed significantly shorter FFT times compared to the saline group. Epithelial damage scores, indicating greater injury, were higher in the saline group, whereas the NSC group exhibited greater epithelial thickness. Immunohistochemical analysis revealed a significantly higher number of olfactory marker protein-expressing cells in the NSC group. GFP + cells were observed in olfactory bulb (OB) and olfactory epithelium (OE) in the NSC group. PCR confirmed the presence of the GFP gene in the OE of NSC-transplanted mice. Intranasal NSCs promoted functional recovery and GFP + cell integration, supporting further research into their therapeutic potential for olfactory dysfunction.

摘要

本研究旨在探讨鼻内移植神经干细胞(NSCs)对嗅觉缺失诱导小鼠的疗效。该研究纳入了24只雄性小鼠。预先进行了食物寻找试验(FFT)以确认所有小鼠嗅觉功能正常。然后将小鼠随机分为两组(第1组和第2组),并用3-甲基吲哚(3-MI)诱导嗅觉缺失。在注射3-MI后的第一周(第1周),第1组小鼠接受鼻内生理盐水注射,而第2组小鼠接受鼻内NSCs注射。NSCs取自绿色荧光蛋白(GFP)转基因小鼠。通过每周一次的FFT评估嗅觉功能。在给予NSC或生理盐水后一周(第2周),每组随机选择一半小鼠并处死以进行组织学检查。其余小鼠在第4周处死以进行组织学检查。在第4周时,还通过聚合酶链反应(PCR)检查了所有小鼠的嗅觉上皮,以检测GFP+细胞。与生理盐水组相比,NSC组的FFT时间明显缩短。生理盐水组的上皮损伤评分更高,表明损伤更严重,而NSC组的上皮厚度更大。免疫组织化学分析显示,NSC组中表达嗅觉标记蛋白的细胞数量明显更多。在NSC组的嗅球(OB)和嗅觉上皮(OE)中观察到了GFP+细胞。PCR证实了NSC移植小鼠的OE中存在GFP基因。鼻内NSCs促进了功能恢复和GFP+细胞整合,支持对其治疗嗅觉功能障碍潜力的进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f404/12084376/f5b94840e1fa/41598_2025_1358_Fig1_HTML.jpg

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