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骨髓间充质干细胞在豚鼠动物模型中治疗顺铂诱导的感音神经性听力损失的潜力。

The potential of bone marrow derived mesenchymal stem cells in treating cisplatin induced sensorineural hearing loss in a guinea pig animal model.

作者信息

Abdelwahed Mohamed Hassan Ali Elsayed, Badreldin Mohamed Hussien, Ibrahim Ibrahim Hassan, Zittoon Reham Farouk, Galhom Rania A, Mohammed Sally S, Ashry Yehia Mohamed

机构信息

ENT Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

ENT Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

出版信息

Tissue Cell. 2025 Apr;93:102703. doi: 10.1016/j.tice.2024.102703. Epub 2024 Dec 30.

Abstract

BACKGROUND

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Current solutions for SNHL, including hearing aids, cochlear implants, and hearing assistive devices, do not provide consistent results and fail to address the underlying pathology of hair cell and ganglion cell damage. Stem cell therapy is a cornerstone in regenerative medicine. It provides new hope to treat SNHL by replacing/regenerating damaged hair cells and ganglion cells. Mesenchymal stem cells are an interesting choice in stem cell therapy.

AIM OF THE WORK

Evaluation of bone marrow derived mesenchymal stem cell (BM-MSC) transplantation to improve SNHL management.

METHODS

An experimental study was conducted using 40 recipient guinea pigs, randomly divided into four groups, along with 4 donor guinea pigs for bone marrow harvesting to isolate BM-MSC. Group I (12 animals) served as the control, receiving neither ototoxic drugs nor stem cell treatment. Group II (12 animals) received intraperitoneal cisplatin (1.5 mg/kg/day for 8 days) to induce sensorineural hearing loss, but no stem cell treatment. Group III (12 animals) received IP cisplatin to induce SNHL, followed by BM-MSC transplantation via round window injection one week later. Groups I, II, and III were euthanized 5 weeks after the last cisplatin injection, and their cochleae were examined using light microscopy, scanning electron microscopy, and fluorescent light microscopy to assess the effect of stem cell transplantation on the recovery of neurosensory tissue in the cochlea after cisplatin treatment. Group IV (4 animals) received IP cisplatin to induce SNHL, followed by transplantation of fluorescein-labeled BM-MSC (FLBM-MSC) via round window injection one week later and were euthanized after one week to study stem cell migration and homing.

RESULTS

Light Microscopy: Group I exhibited a normal structure in the organ of Corti, spiral ganglion, and stria vascularis. In contrast, Group II demonstrated degeneration in these areas. Group III showed a preserved structure in the organ of Corti, spiral ganglion, and stria vascularis, with statistically significant differences compared to Group II (p < .05). Scanning Electron Microscopy: Group I displayed normal ultrastructure of the organ of Corti, while Group II showed a loss of outer hair cells. Group III demonstrated preserved ultrastructure of the organ of Corti. Fluorescent Light Microscopy: In Group IV, transplanted cells were observed to home into the cochlear lateral wall, organ of Corti, and spiral ganglion.

CONCLUSION

The study showed that BM-MSCs, delivered via round window injection, can migrate to cochlear regions and protect key structures after cisplatin-induced SNHL in guinea pigs, suggesting their potential as a treatment for SNHL.

摘要

背景

感音神经性听力损失(SNHL)是全球最常见的感觉缺陷。目前治疗SNHL的方法,包括助听器、人工耳蜗和听力辅助设备,效果并不一致,且未能解决毛细胞和神经节细胞损伤的潜在病理问题。干细胞疗法是再生医学的基石。它通过替代/再生受损的毛细胞和神经节细胞为治疗SNHL提供了新希望。间充质干细胞是干细胞疗法中一个有趣的选择。

工作目的

评估骨髓源性间充质干细胞(BM-MSC)移植对改善SNHL治疗的效果。

方法

进行一项实验研究,使用40只受体豚鼠,随机分为四组,另有4只供体豚鼠用于采集骨髓以分离BM-MSC。第一组(12只动物)作为对照,既不接受耳毒性药物也不接受干细胞治疗。第二组(12只动物)腹腔注射顺铂(1.5 mg/kg/天,共8天)以诱导感音神经性听力损失,但不进行干细胞治疗。第三组(12只动物)腹腔注射顺铂诱导SNHL,一周后通过圆窗注射进行BM-MSC移植。第一组、第二组和第三组在最后一次注射顺铂5周后实施安乐死,并使用光学显微镜、扫描电子显微镜和荧光显微镜检查其耳蜗,以评估干细胞移植对顺铂治疗后耳蜗神经感觉组织恢复的影响。第四组(4只动物)腹腔注射顺铂诱导SNHL,一周后通过圆窗注射荧光素标记的BM-MSC(FLBM-MSC),一周后实施安乐死以研究干细胞的迁移和归巢。

结果

光学显微镜检查:第一组耳蜗的柯蒂氏器、螺旋神经节和血管纹结构正常。相比之下,第二组这些区域出现退化。第三组柯蒂氏器、螺旋神经节和血管纹结构得以保留,与第二组相比有统计学显著差异(p < 0.05)。扫描电子显微镜检查:第一组柯蒂氏器超微结构正常,而第二组外毛细胞缺失。第三组柯蒂氏器超微结构得以保留。荧光显微镜检查:在第四组中,观察到移植细胞归巢至耳蜗外侧壁、柯蒂氏器和螺旋神经节。

结论

该研究表明,通过圆窗注射递送的BM-MSC可迁移至耳蜗区域,并在豚鼠顺铂诱导的SNHL后保护关键结构,提示其作为SNHL治疗方法的潜力。

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