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应用于纤维蛋白胶的脂肪源性间充质干细胞促进周围神经再生。

Adipose-Derived Mesenchymal Stem Cells Applied in Fibrin Glue Stimulate Peripheral Nerve Regeneration.

作者信息

Masgutov Ruslan, Masgutova Galina, Mullakhmetova Adelya, Zhuravleva Margarita, Shulman Anna, Rogozhin Alexander, Syromiatnikova Valeriya, Andreeva Dina, Zeinalova Alina, Idrisova Kamilla, Allegrucci Cinzia, Kiyasov Andrey, Rizvanov Albert

机构信息

OpenLab Gene and Cell Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.

Department of Orthopaedics, Republic Clinical Hospital, Kazan, Russia.

出版信息

Front Med (Lausanne). 2019 Apr 9;6:68. doi: 10.3389/fmed.2019.00068. eCollection 2019.

Abstract

Mesenchymal stem cells (MSCs) hold a great promise for cell therapy. To date, they represent one of the best choices for the treatment of post-traumatic injuries of the peripheral nervous system. Although autologous can be easily transplanted in the injured area, clinical advances in this filed have been impaired by lack of preservation of graft cells into the injury area after transplantation. Indeed, cell viability is not retained after injection into the blood stream, and cells injected directly into the area of injury either are washed off or inhibit regeneration through scar formation and neuroma development. This study proposes a new way of MSCs delivery to the area of traumatic injury by using fibrin glue, which not only fixes cells at the site of application but also provides extracellular matrix support. Using a sciatic nerve injury model, MSC derived from adipose tissue embedded in fibrin glue were able to enter the nerve and migrate mainly retrogradely after transplantation. They also demonstrated a neuroprotective effect on DRG L5 sensory neurons and stimulated axon growth and myelination. Post-traumatic changes of the sensory neuron phenotype were also improved. Importantly, MSCs stimulated nerve angiogenesis and motor function recovery. Therefore, our data suggest that MSC therapy using fibrin glue is a safe and efficient method of cell transplantation in cases of sciatic nerve injury, and that this method of delivery of regeneration stimulants could be beneficial for the successful treatment of other central and peripheral nervous system conditions.

摘要

间充质干细胞(MSCs)在细胞治疗方面具有巨大潜力。迄今为止,它们是治疗外周神经系统创伤后损伤的最佳选择之一。尽管自体间充质干细胞可以很容易地移植到损伤区域,但该领域的临床进展因移植后移植细胞在损伤区域的留存率低而受到阻碍。事实上,将细胞注入血流后其活力无法维持,直接注入损伤区域的细胞要么被冲走,要么通过瘢痕形成和神经瘤发展抑制再生。本研究提出了一种利用纤维蛋白胶将间充质干细胞递送至创伤损伤区域的新方法,这种方法不仅能将细胞固定在应用部位,还能提供细胞外基质支持。使用坐骨神经损伤模型,将来源于脂肪组织并嵌入纤维蛋白胶的间充质干细胞移植后,能够进入神经并主要逆行迁移。它们还对L5背根神经节(DRG)感觉神经元表现出神经保护作用,并刺激轴突生长和髓鞘形成。感觉神经元表型的创伤后变化也得到改善。重要的是,间充质干细胞刺激了神经血管生成和运动功能恢复。因此,我们的数据表明,在坐骨神经损伤病例中,使用纤维蛋白胶的间充质干细胞治疗是一种安全有效的细胞移植方法,并且这种再生刺激剂的递送方法可能有利于成功治疗其他中枢和外周神经系统疾病。

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