骨髓间充质干细胞在豚鼠动物模型中治疗顺铂诱导的感觉神经性听力损失的潜力

IF 2.7 4区 生物学 Q1 ANATOMY & MORPHOLOGY Tissue & cell Pub Date : 2024-12-30 DOI:10.1016/j.tice.2024.102703
Mohamed Hassan Ali Elsayed Abdelwahed, Mohamed Hussien Badreldin, Ibrahim Hassan Ibrahim, Reham Farouk Zittoon, Rania A Galhom, Sally S Mohammed, Yehia Mohamed Ashry
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引用次数: 0

摘要

背景:感觉神经性听力损失(SNHL)是世界范围内最常见的感觉缺陷。目前SNHL的解决方案,包括助听器、人工耳蜗和助听器,不能提供一致的结果,也不能解决毛细胞和神经节细胞损伤的潜在病理。干细胞治疗是再生医学的基石。它通过替换/再生受损的毛细胞和神经节细胞为治疗SNHL提供了新的希望。间充质干细胞是干细胞治疗中一个有趣的选择。研究目的:评价骨髓间充质干细胞(BM-MSC)移植改善SNHL治疗的效果。方法:选取40只受体豚鼠,随机分为4组,同时选取4只供体豚鼠,采集骨髓分离BM-MSC。第一组(12只)作为对照组,既不接受耳毒性药物治疗,也不接受干细胞治疗。II组(12只动物)腹腔注射顺铂(1.5 mg/kg/天,连续8天)诱导感音神经性听力损失,但不进行干细胞治疗。III组(12只动物)采用顺铂诱导SNHL, 1周后进行BM-MSC圆窗注射移植。I、II、III组在最后一次顺铂注射5周后安乐死,通过光镜、扫描电镜、荧光显微镜检查耳蜗,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。IV组(4只)接受顺铂诱导SNHL, 1周后圆窗注射荧光素标记的骨髓间充质干细胞(FLBM-MSC)移植,1周后安乐死,研究干细胞迁移和归巢。结果:光镜观察:ⅰ组大鼠Corti、螺旋神经节、血管纹等脏器结构正常。相比之下,第二组在这些区域表现出退化。III组在Corti、螺旋神经节、血管纹等脏器中均有保存结构,与II组相比差异有统计学意义(p )。结论:本研究表明,顺铂诱导的豚鼠SNHL后,经圆窗注射给药的脑间质干细胞可迁移至耳蜗区域并保护关键结构,提示其治疗SNHL的潜力。
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The potential of bone marrow derived mesenchymal stem cells in treating cisplatin induced sensorineural hearing loss in a guinea pig animal model.

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.

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来源期刊
Tissue & cell
Tissue & cell 医学-解剖学与形态学
CiteScore
3.90
自引率
0.00%
发文量
234
期刊介绍: Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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