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[一种用于将骨髓源性干细胞作为薄层微创移植到视网膜下和脉络膜血管外间隙以治疗视网膜变性的新型系统]

[A novel system for minimally invasive transplantation of bone marrow derived stem cells as a thin layer in the subretina and extravascular spaces of the choroid--for treatment of retinal degeneration].

作者信息

Rotenstreich Ygal, Tzameret Adi, Kalish Sapir E, Belkin Michael, Meir Amilia, Treves Avraham J, Naglera Arnon, Sher Ifat

出版信息

Harefuah. 2015 Feb;154(2):84-8, 138.

Abstract

BACKGROUND

Incurable retinal degenerations affect millions worldwide. Stem cell transplantation rescued visual functions in animal models of retinal degeneration. In those studies, cells were transplanted in subretinal "blebs". A limited number of cells could be injected and photoreceptor rescue was restricted to areas in proximity to the injection sites.

PURPOSE

To develop a minimally-invasive surgical system for stem cell transplantation in the subretina and extravascular spaces of the choroid.

METHODS

A novel syringe with flexible needle and adjustable pin was developed. Human bone marrow mesenchymal stem cells [hBM-MSCs) were transplanted in the eyes of RCS rats and NZW rabbits through a longitudinal triangular scleral incision. No immunosuppressants were used. Retinal function was determined by electroretinogram analysis and retinal structure was determined by histological analysis and optical coherence tomography (OCT).

RESULTS

Transplanted cells were identified as a thin layer across the subretina and extravascular spaces of the choroid. In RCS rats, cell transplantation delayed photoreceptor degeneration across the entire retina and significantly enhanced retinal functions. No changes in retinal functions were recorded in rabbits following transplantation. No retinal detachment or choroidal hemorrhages were observed.

CONCLUSIONS

The novel syringe facilitates cell transplantation across the subretina and extravascular spaces of the choroid using a minimally-invasive procedure. Human BM-MSC transplantation using this system ameliorates retinal degeneration in the animal model.

DISCUSSION

This new transplantation system may increase the therapeutic effect of other cell-based therapies and therapeutic agents. This study is expected to lead directly to phase I clinical trials for autologous hBM-MSCs transplantation in patients with retinal degeneration.

摘要

背景

无法治愈的视网膜变性影响着全球数百万人。干细胞移植在视网膜变性动物模型中挽救了视觉功能。在这些研究中,细胞被移植到视网膜下“泡”中。能够注射的细胞数量有限,并且光感受器的挽救仅限于注射部位附近的区域。

目的

开发一种用于在视网膜下和脉络膜血管外间隙进行干细胞移植的微创手术系统。

方法

研制了一种带有柔性针头和可调节销的新型注射器。通过纵向三角形巩膜切口将人骨髓间充质干细胞(hBM-MSCs)移植到RCS大鼠和新西兰白兔的眼中。未使用免疫抑制剂。通过视网膜电图分析确定视网膜功能,通过组织学分析和光学相干断层扫描(OCT)确定视网膜结构。

结果

移植的细胞在视网膜下和脉络膜血管外间隙形成一层薄组织。在RCS大鼠中,细胞移植延缓了整个视网膜光感受器的退化,并显著增强了视网膜功能。移植后兔子的视网膜功能未记录到变化。未观察到视网膜脱离或脉络膜出血。

结论

这种新型注射器通过微创程序便于细胞在视网膜下和脉络膜血管外间隙移植。使用该系统进行人骨髓间充质干细胞移植可改善动物模型中的视网膜变性。

讨论

这种新的移植系统可能会提高其他基于细胞的疗法和治疗药物的治疗效果。这项研究有望直接促成针对视网膜变性患者进行自体人骨髓间充质干细胞移植的I期临床试验。

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