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给嗅觉缺失小鼠注射脂肪组织来源的间充质干细胞和骨髓来源的间充质干细胞。

Administration of adipose tissue-derived mesenchymal stem cells and bone marrow-derived mesenchymal stem cells in anosmic mice.

作者信息

Hazir Burak, Ceylan Alper, Bağriaçik Emin Ümit, Dayanir Duygu, Öğüt Betül, Örüklü Nihan, Yalçin Mücahit, Şimşek Berkay, Şahin Muammer Melih

机构信息

Department of Otorhinolaryngology, Ankara City Hospital, Ankara, Turkiye.

Department of Otorhinolaryngology, Faculty of Medicine, Gazi University, Ankara, Turkiye.

出版信息

Turk J Med Sci. 2025 Apr 5;55(3):792-801. doi: 10.55730/1300-0144.6028. eCollection 2025.

Abstract

BACKGROUND/AIM: Anosmia, a serious condition that affects the sense of smell, has no universally agreed-upon treatment. Adult stem cells are considered a potential option for treating anosmia. This study aims to evaluate the efficacy of mesenchymal stem cells derived from different tissues in an anosmic mouse model induced by 3-methylindole (3-MI).

MATERIALS AND METHODS

In our study, 36 mice with 3-MI-induced anosmia were divided into subgroups. Anosmia was confirmed by performing a food-finding test (FFT) in each group. Intranasal phosphate-buffered saline was administered to the first group, adipose tissue-derived mesenchymal stem cells (ADSCs) to the second group, and bone marrow-derived mesenchymal stem cells (BMSCs) to the third group. Stem cells were obtained from green fluorescent protein (GFP)-transgenic mice. Olfactory function was evaluated weekly using the FFTs. Mice were sacrificed at the second and fourth weeks following 3-MI injection and examined histopathologically.

RESULTS

Compared to the control group, stem cell-transplanted groups demonstrated significantly improved food-finding times measured at week 2 and week 4 FFTs following the 3-MI injection (respectively; p = 0.001, p = 0.008). Additionally, increased olfactory marker protein expression and olfactory epithelial thickness, along with reduced epithelial damage, were observed in the stem cell-transplanted groups compared to the control group (p < 0.05). Histologically, BMSCs showed greater efficacy than ADSCs in promoting olfactory regeneration. Furthermore, GFP+ cells were detected in the olfactory epithelium and olfactory bulbs of the stem cell-transplanted groups.

CONCLUSION

It was observed that intranasally transplanted stem cells could reach the damaged olfactory region and enhance olfactory regeneration and functional recovery. Both ADSCs and BMSCs were effective in treatment and appear to be promising therapeutic modalities.

摘要

背景/目的:嗅觉丧失是一种影响嗅觉的严重病症,目前尚无普遍认可的治疗方法。成体干细胞被认为是治疗嗅觉丧失的一种潜在选择。本研究旨在评估源自不同组织的间充质干细胞在3-甲基吲哚(3-MI)诱导的嗅觉丧失小鼠模型中的疗效。

材料与方法

在我们的研究中,36只由3-MI诱导嗅觉丧失的小鼠被分为亚组。通过在每组中进行食物寻找试验(FFT)来确认嗅觉丧失。第一组经鼻给予磷酸盐缓冲盐水,第二组给予脂肪组织来源的间充质干细胞(ADSC),第三组给予骨髓来源的间充质干细胞(BMSC)。干细胞取自绿色荧光蛋白(GFP)转基因小鼠。每周使用FFT评估嗅觉功能。在注射3-MI后的第二周和第四周处死小鼠,并进行组织病理学检查。

结果

与对照组相比,干细胞移植组在3-MI注射后第2周和第4周的FFT中测得的食物寻找时间显著改善(分别为p = 0.001,p = 0.008)。此外,与对照组相比,干细胞移植组观察到嗅觉标记蛋白表达增加、嗅觉上皮厚度增加以及上皮损伤减少(p < 0.05)。组织学上,BMSC在促进嗅觉再生方面显示出比ADSC更高的疗效。此外,在干细胞移植组的嗅觉上皮和嗅球中检测到GFP+细胞。

结论

观察到经鼻移植的干细胞可到达受损的嗅觉区域并增强嗅觉再生和功能恢复。ADSC和BMSC在治疗中均有效,似乎是有前景的治疗方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/658a/12270316/fe02b505d9be/tjmed-55-03-792f1.jpg

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