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经血管内皮生长因子(VEGF)和胶质细胞源性神经营养因子(GDNF)基因修饰的人脐带血单个核细胞移植后损伤脊髓组织的电生理、形态学及超微结构特征

Electrophysiological, Morphological, and Ultrastructural Features of the Injured Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes.

作者信息

Mukhamedshina Y O, Gilazieva Z E, Arkhipova S S, Galieva L R, Garanina E E, Shulman A A, Yafarova G G, Chelyshev Y A, Shamsutdinova N V, Rizvanov A A

机构信息

Kazan Federal University, Kazan, Russia.

Kazan State Medical University, Kazan, Russia.

出版信息

Neural Plast. 2017;2017:9857918. doi: 10.1155/2017/9857918. Epub 2017 Mar 21.

Abstract

In this study, we examined the efficacy of human umbilical cord blood mononuclear cells (hUCB-MCs), genetically modified with the VEGF and GDNF genes using adenoviral vectors, on posttraumatic regeneration after transplantation into the site of spinal cord injury (SCI) in rats. Thirty days after SCI, followed by transplantation of nontransduced hUCB-MCs, we observed an improvement in H (latency period, LP) and M() waves, compared to the group without therapy after SCI. For genetically modified hUCB-MCs, there was improvement in of M wave and LP of both the M and H waves. The ratio between of the H and M waves (H/M) demonstrated that transplantation into the area of SCI of genetically modified hUCB-MCs was more effective than nontransduced hUCB-MCs. Spared tissue and myelinated fibers were increased at day 30 after SCI and transplantation of hUCB-MCs in the lateral and ventral funiculi 2.5 mm from the lesion epicenter. Transplantation of hUCB-MCs genetically modified with the VEGF and GNDF genes significantly increased the number of spared myelinated fibers (22-fold, > 0.01) in the main corticospinal tract compared to the nontransduced ones. HNA cells with the morphology of phagocytes and microglia-like cells were found as compact clusters or cell bridges within the traumatic cavities that were lined by GFAP host astrocytes. Our results show that hUCB-MCs transplanted into the site of SCI improved regeneration and that hUCB-MCs genetically modified with the VEGF and GNDF genes were more effective than nontransduced hUCB-MCs.

摘要

在本研究中,我们检测了使用腺病毒载体经血管内皮生长因子(VEGF)和胶质细胞源性神经营养因子(GDNF)基因修饰的人脐带血单个核细胞(hUCB - MCs),在移植到大鼠脊髓损伤(SCI)部位后对创伤后再生的疗效。脊髓损伤30天后,在未转导的hUCB - MCs移植后,与脊髓损伤后未接受治疗的组相比,我们观察到H波(潜伏期,LP)和M波的改善。对于基因修饰的hUCB - MCs,M波的 以及M波和H波的LP均有改善。H波和M波的 之比(H/M)表明,基因修饰的hUCB - MCs移植到脊髓损伤区域比未转导的hUCB - MCs更有效。在脊髓损伤及hUCB - MCs移植后30天,距损伤中心2.5毫米处的外侧和腹侧脊髓白质中, spared组织和有髓纤维增加。与未转导的hUCB - MCs相比,经VEGF和GNDF基因修饰的hUCB - MCs移植显著增加了主要皮质脊髓束中有髓纤维的数量(22倍,P>0.01)。发现具有吞噬细胞和小胶质细胞样细胞形态的HNA细胞,在由GFAP宿主星形胶质细胞衬里的创伤腔内呈紧密簇状或细胞桥状。我们的结果表明,移植到脊髓损伤部位的hUCB - MCs改善了再生,并且经VEGF和GNDF基因修饰的hUCB - MCs比未转导的hUCB - MCs更有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/740e/5379091/83b753fe4683/NP2017-9857918.001.jpg

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