骨髓间充质干细胞来源的外泌体或其与锌联合应用在大鼠舌咽神经双侧切断术后退化的轮廓乳头再生中的作用。

Regenerative potentials of bone marrow mesenchymal stem cells derived exosomes or its combination with zinc in recovery of degenerated circumvallate papilla following surgical bilateral transection of glossopharyngeal nerve in rats.

机构信息

Oral Biology Department, College of Oral and Dental Surgery, Misr University for Science and Technology, Giza, 12568, Egypt.

Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, 115533, Egypt.

出版信息

BMC Oral Health. 2024 Oct 30;24(1):1320. doi: 10.1186/s12903-024-05050-7.

Abstract

BACKGROUND

Taste buds' innervation is necessary to sustain their cell turnover, differentiated taste buds and nerve fibers in circumvallate papilla (CVP) disappear following glossopharyngeal nerve transection. Normally, taste buds recover to baseline number in about 70 days. Bone marrow stem cell (BM-MSC) derived exosomes or their combination with Zinc chloride are used to assess their potential to speed up the regeneration process of CVP following bilateral deafferentation.

METHODS

Twenty-eight male Sprague-Dawley rats were randomly divided into four groups; Group I: subjected to sham operation followed by IP injection of saline. The other experimental groups (II, III and IV) were subjected to surgical bilateral transection of glossopharyngeal nerve. Group II received single IP injection of saline. Group III received single IV injection of BM-MSC-derived exosomes (100 µg). Group IV received single IV injection of BM-MSC-derived exosomes and single IP injection of zinc chloride (5 mg/kg). After 28 days, CVP was dissected and prepared for histological and histomorphometric analysis, RT-PCR for cytokeratin 8 gene expression, ELISA to assess protein level of brain-derived neurotrophic factor, redox state analysis of malondialdehyde and glutathione content, followed by statistical analysis.

RESULTS

Histopathologically, group II exhibited great tissue damage with marked reduction in taste buds and signs of degeneration in the remaining ones. Group III was close to control group with marked improvement in taste buds' number and structure. Group IV showed inferior results when compared to group III, with many immature taste buds and signs of degeneration. Statistical results showed that groups I and III have significantly higher values than groups II and IV regarding taste buds' number, cytokeratin 8, and reduced glutathione. However, malondialdehyde demonstrated high significant values in group IV compared to groups I and III. Regarding brain-derived neurotrophic factor, group III had significantly higher values than group II.

CONCLUSION

BM-MSC-derived exosomes have superior regenerative potentials in acceleration of CVP and nerve healing following bilateral transection of glossopharyngeal nerve in contrary to its combination with zinc chloride.

摘要

背景

味觉感受器的神经支配对于维持其细胞更新至关重要,因此,当切断舌咽神经后,环状乳头(CVP)中的味觉感受器和神经纤维会消失。正常情况下,大约 70 天后,味觉感受器会恢复到基线数量。骨髓间充质干细胞(BM-MSC)衍生的外泌体或其与氯化锌的组合,用于评估它们在双侧去传入后加速 CVP 再生过程的潜力。

方法

28 只雄性 Sprague-Dawley 大鼠随机分为四组;I 组:假手术,随后腹腔注射生理盐水。其他实验组(II、III 和 IV 组)行双侧切断舌咽神经手术。II 组腹腔单次注射生理盐水。III 组单次静脉注射 BM-MSC 衍生的外泌体(100µg)。IV 组单次静脉注射 BM-MSC 衍生的外泌体和单次腹腔注射氯化锌(5mg/kg)。28 天后,解剖 CVP,进行组织学和组织形态计量学分析、细胞角蛋白 8 基因表达的 RT-PCR、脑源性神经营养因子蛋白水平的 ELISA 检测、丙二醛和谷胱甘肽含量的氧化还原状态分析,然后进行统计学分析。

结果

组织病理学上,II 组组织损伤严重,味觉感受器明显减少,剩余味觉感受器有退行性变迹象。III 组接近对照组,味觉感受器数量和结构明显改善。与 III 组相比,IV 组结果较差,有许多不成熟的味觉感受器和退行性变迹象。统计学结果表明,与 II 组和 IV 组相比,I 组和 III 组的味觉感受器数量、细胞角蛋白 8 和还原型谷胱甘肽显著升高。然而,与 I 组和 III 组相比,IV 组的丙二醛含量显著升高。关于脑源性神经营养因子,III 组明显高于 II 组。

结论

与氯化锌联合使用相比,BM-MSC 衍生的外泌体在加速双侧切断舌咽神经后的 CVP 和神经愈合方面具有更好的再生潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9383/11523770/8704d2b722ca/12903_2024_5050_Fig1_HTML.jpg

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