摘要
背景:神经退行性疾病包括一组迄今尚未治疗的疾病。干细胞为基础的治疗提供了很大的希望和承诺。然而,干细胞移植与某些缺点有关,如移植细胞的定向迁移,植入和存活较差。 材料和方法:外来体,一种由包括干细胞在内的所有细胞类型释放的细胞外囊泡,为干细胞移植提供了一种替代方法。外来体携带大量的生物分子,并且涉及在受损组织的修复/再生中表现出显着的益处。因此,外来体提供替代的治疗方法作为细胞移植的替代物。为了将外来体用于治疗目的,必须评估合适的传代次数和剂量以避免可能的细胞毒性作用。在此,我们从大鼠骨髓间充质干细胞(BM-MSC)的不同代外来体中分离了外来体,并且在体外兴奋毒性模型中分析了BM-MSC外泌体的神经保护潜力。 结果:我们的研究结果表明从大鼠BM-MSC早期分离的外泌体展现出更有效的神经保护潜力,而不是晚期传代衍生的外来体。此外,外泌体的神经保护功效是剂量依赖性的。即发现较低剂量的外来体是神经保护的,而较高剂量的外来体(来自后来的传代)被发现对神经元有害。早期通过外源体通过抗凋亡,抗坏死和抗氧化机制保护神经元。 结论:我们的研究表明,成体干细胞衍生的外泌体可能是一种潜在的治疗剂,赋予神经退行性疾病如阿尔茨海默病的神经保护作用。
关键词: 海马,骨髓,间充质,外泌体,神经变性,神经保护。
Current Gene Therapy
Title:Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis
Volume: 17 Issue: 5
关键词: 海马,骨髓,间充质,外泌体,神经变性,神经保护。
摘要: Background: Neurodegenerative diseases comprise a group of disorders for which no treatment is available till date. Stem cell based therapy offers great hope and promise. However, stem cell transplantation is associated with certain disadvantages like poor targeted migration, engraftment and survival of the transplanted cells.
Material & Method: Exosomes, a type of extracellular membrane vesicle released by all cell types including stem cells, offer an alternative to stem cell transplantation. Exosome carry a wide array of biomolecules and are implicated in exhibiting substantial benefits in the repair/regeneration of the injured tissue. Thus, exosomes offer an alternative therapeutic approach as a substitute of cell transplantation. In order to utilize exosomes for therapeutic purpose, it is essential to evaluate the appropriate passage number and the dosage to avoid possible cytotoxic effects. Here, we isolated exosomes from different passages of rat bone marrow mesenchymal stem cells (BM-MSC) and analysed the neuroprotective potential of BM-MSC exosomes in an in vitro model of excitotoxicity.
Result: Our results demonstrated that the exosomes isolated from early passage of rat BM-MSC exhibited more efficient neuroprotective potential as opposed to later passages derived exosomes. Furthermore, the neuroprotective efficacy of exosome is dosage dependent. i.e. the lower dosage of exosomes was found to be neuroprotective, whereas higher dosage of exosomes (from later passages) was found to be detrimental to neurons. The early passage derived exosomes protected neurons through anti-apoptotic, anti-necrotic and anti-oxidant mechanisms.
Conclusion: Our study suggests that adult stem cells derived exosomes could be a potential therapeutic agent to confer neuroprotection in neurodegenerative diseases like Alzheimer's disease.
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Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis, Current Gene Therapy 2017; 17 (5) . https://dx.doi.org/10.2174/1566523218666180125091952
DOI https://dx.doi.org/10.2174/1566523218666180125091952 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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