Zakaria Ahmed, Sultan Nessma, Nabil Nesreen, Elgamily Mahitabe
Egyptian Ministry of Health, Mansoura, Egypt.
Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt.
Oral Maxillofac Surg. 2025 Jan 17;29(1):39. doi: 10.1007/s10006-025-01331-9.
OBJECTIVE: A nanometer-sized vesicles originating from bone marrow mesenchymal stem cells (BMMSCs), called exosomes, have been extensively recognized. This study defines the impact of BMMSCs and their derived exosomes on proliferation, apoptosis and oxidative stress (OS) levels of CP-induced parotid salivary gland damage. METHODS: BMMSCs were isolated from the tibia of four white albino rats and further characterized by flowcytometric analysis. BMMSCs-derived exosomes were harvested and underwent characterization using transmission electron microscopy (TEM), western blot analysis and BCA assay. Fifty-six healthy white albino male rats weighting from 200 to 250 g were allocated into 4 groups (n = 14); Group I, rats received phosphate buffered saline (PBS), group II, rats were intraperitoneally injected with CP, group III& IV received CP and after 3 days they were intravenously injected with either BMMSCs (group III) or BMMSCs-exosomes (group IV). Histological, and immunohistochemical studies using proliferating cell nuclear antigen (PCNA) were done after 7 and 14 days. The OS was measured using malondialdehyde (MDA) and apoptosis was measured by annexin V-FITC/PI. RESULTS: BMMSCs and exosomes treated groups showed better histological features approximating the normal architecture of the control group. The percentage of PCNA positively stained cells were significantly higher in the exosomes treated group in comparison to all other groups. MDA assay test revealed that the exosomes were able to reduce the OS when compared to the cell-based therapy using BMMSCs. Annexin V revealed that BMMSCs-exosomes significantly reduced the percentage of apoptotic cells compared to other treated groups. CONCLUSIONS: BMMSCs-exosomes could improve the CP-induced cytotoxicity in rats' parotid salivary gland.
目的:源自骨髓间充质干细胞(BMMSCs)的纳米级囊泡,即外泌体,已得到广泛认可。本研究确定了BMMSCs及其衍生的外泌体对环磷酰胺(CP)诱导的腮腺唾液腺损伤的增殖、凋亡和氧化应激(OS)水平的影响。 方法:从四只白色白化大鼠的胫骨中分离出BMMSCs,并通过流式细胞术分析进一步鉴定。收集BMMSCs衍生的外泌体,并使用透射电子显微镜(TEM)、蛋白质免疫印迹分析和BCA测定法进行表征。将56只体重在200至250 g之间的健康白色白化雄性大鼠分为4组(n = 14);第一组,大鼠接受磷酸盐缓冲盐水(PBS),第二组,大鼠腹腔注射CP,第三组和第四组接受CP,3天后分别静脉注射BMMSCs(第三组)或BMMSCs外泌体(第四组)。7天和14天后进行组织学和使用增殖细胞核抗原(PCNA)的免疫组织化学研究。使用丙二醛(MDA)测量OS,通过膜联蛋白V-FITC/PI测量凋亡。 结果:BMMSCs和外泌体治疗组显示出更好的组织学特征,接近对照组的正常结构。与所有其他组相比,外泌体治疗组中PCNA阳性染色细胞的百分比显著更高。MDA测定试验表明,与使用BMMSCs的细胞疗法相比,外泌体能够降低OS。膜联蛋白V显示,与其他治疗组相比,BMMSCs外泌体显著降低了凋亡细胞的百分比。 结论:BMMSCs外泌体可以改善CP诱导的大鼠腮腺唾液腺细胞毒性。
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