摘要
前言:间充质干细胞(MSC)治疗近年来受到广泛关注。尽管MSC治疗神经退行性疾病后的功能结果是令人信服的,但功能恢复的各种机制仍在争论中。然而,最近的研究令人信服地证明,MSC治疗后的恢复可以用MSC分泌体本身来重申,从而将教条从细胞治疗转变为基于细胞的治疗。除了多种功能蛋白外,干细胞分泌体还包括胞外膜囊泡,如外小体。具有“Nano”大小的外显子引起了人们极大的兴趣,因为它们比宏观大小的细胞或生长因子更容易通过血脑屏障。外显子作为细胞之间的一种货物,使靶细胞发生重大变化。随着外体细胞的重要性日益显现,对其神经保护潜力进行综合研究,与常规共培养或全条件培养基治疗相比,是十分必要的。目的:本研究旨在比较MSC衍生外体与MSC-条件培养基或神经元-MSC-共培养系统对红藻氨酸诱导的兴奋性神经毒性的保护作用。本研究还比较了两种MSC,即神经嵴衍生人牙髓干细胞(HDPSC)和人骨髓间充质干细胞(HBM-MSC)的外体/条件培养基/共培养对神经保护作用,以确定治疗神经退行性疾病的合适MSC来源。结果:MSC-Exosome的神经保护作用与MSC-条件培养基或神经元-MSC共培养系统一样有效,三种方法均能通过激活细胞存活PI3K-B-细胞淋巴瘤-2(Bcl-2)途径,上调宿主内源性生长因子的表达,防止细胞凋亡。结论:因此,目前的研究强调了用“Nano”大小的外显子来治疗神经退行性疾病的可能性,而不是移植数十亿的干细胞。
关键词: 间充质干细胞,神经保护,外显子,海马,分泌体,PI3K-B细胞淋巴瘤-2通路。
Erratum In:
Neuroprotection by Human Dental Pulp Mesenchymal
Stem Cells: From Billions to Nano
Current Gene Therapy
Title:Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano
Volume: 18 Issue: 5
关键词: 间充质干细胞,神经保护,外显子,海马,分泌体,PI3K-B细胞淋巴瘤-2通路。
摘要: Introduction: Mesenchymal Stem Cell (MSC) therapy in recent years has gained significant attention. Though the functional outcomes following MSC therapy for neurodegenerative diseases are convincing, various mechanisms for the functional recovery are being debated. Nevertheless, recent studies convincingly demonstrated that recovery following MSC therapy could be reiterated with MSC secretome per se thereby shifting the dogma from cell therapy to cell “based” therapy. In addition to various functional proteins, stem cell secretome also includes extracellular membrane vesicles like exosomes. Exosomes which are of “Nano” size have attracted significant interest as they can pass through the bloodbrain barrier far easily than macro size cells or growth factors. Exosomes act as a cargo between cells to bring about significant alterations in target cells. As the importance of exosomes is getting unveil, it is imperial to carry out a comprehensive study to evaluate the neuroprotective potential of exosomes as compared to conventional co-culture or total condition medium treatments.
Objective: Thus, the present study is designed to compare the neuroprotective potential of MSC derived exosomes with MSC-condition medium or neuron–MSC-co-culture system against kainic acid induced excitotoxicity in in vitro condition. The study also aims at comparing the neuroprotective efficacy of exosomes/condition medium/co-culture of two MSC viz., neural crest derived human Dental Pulp Stem Cells (hDPSC) and human Bone-Marrow Mesenchymal Stem Cells (hBM-MSC) to identify the appropriate MSC source for treating neurodegenerative diseases.
Result: Our results demonstrated that neuroprotective efficacy of MSC-exosomes is as efficient as MSC-condition medium or neuron-MSC co-culture system and treating degenerating hippocampal neurons with all three MSC based approaches could up-regulate host’s endogenous growth factor expressions and prevent apoptosis by activating cell survival PI3K-B-cell lymphoma-2 (Bcl-2) pathway.
Conclusion: Thus, the current study highlights the possibilities of treating neurodegenerative diseases with “Nano” size exosomes as opposed to transplanting billions of stem cells which inherit several disadvantages.
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Cite this article as:
Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano, Current Gene Therapy 2018; 18 (5) . https://dx.doi.org/10.2174/1566523218666180913152615
DOI https://dx.doi.org/10.2174/1566523218666180913152615 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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