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.
Eman Mohamed Salem, Hamdy Rizk, Yara S Abouelela, Abdelbary Prince, Adel Fathy Tohamy, Nawal A Lasheen, Bassant A Ezzat, Sana Mostafa
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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.
背景：味蕾的神经支配是维持味蕾细胞更新的必要条件，在舌咽神经横断后，已分化的味蕾和环状乳头（CVP）的神经纤维会消失。正常情况下，味蕾会在大约70天后恢复到基线数量。骨髓干细胞（BM-MSC）衍生的外泌体或其与氯化锌的结合被用于评估其在双侧舌咽神经切断后加速CVP再生过程的潜力：将 28 只雄性 Sprague-Dawley 大鼠随机分为四组：I 组：进行假手术，然后 IP 注射生理盐水；II 组：进行假手术，然后 IP 注射生理盐水；III 组：进行假手术，然后 IP 注射生理盐水；II 组：进行假手术，然后 IP 注射生理盐水。其他实验组（II、III 和 IV 组）接受手术双侧切断舌咽神经。第二组接受一次生理盐水 IP 注射。第三组接受单次静脉注射源自骨髓间充质干细胞的外泌体（100 µg）。第四组接受单次静脉注射源自骨髓间充质干细胞的外泌体和单次 IP 氯化锌注射（5 毫克/千克）。28天后，解剖CVP并准备进行组织学和组织形态学分析、RT-PCR检测细胞角蛋白8基因表达、ELISA评估脑源性神经营养因子蛋白水平、丙二醛和谷胱甘肽含量的氧化还原状态分析，然后进行统计分析：从组织病理学角度看，II 组的组织损伤严重，味蕾明显减少，剩余的味蕾有退化迹象。第三组接近对照组，味蕾数量和结构明显改善。第四组的结果不如第三组，有许多未成熟的味蕾和退化的迹象。统计结果显示，在味蕾数量、细胞角蛋白 8 和还原型谷胱甘肽方面，I 组和 III 组的数值明显高于 II 组和 IV 组。然而，与 I 组和 III 组相比，IV 组的丙二醛值明显偏高。在脑源性神经营养因子方面，III组的数值明显高于II组：结论：BM-间充质干细胞衍生的外泌体在加速CVP和双侧舌咽神经横断后的神经愈合方面具有更优越的再生潜力，这与它与氯化锌的组合相反。
期刊介绍：
BMC Oral Health is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of disorders of the mouth, teeth and gums, as well as related molecular genetics, pathophysiology, and epidemiology.
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