Transplantation of bone marrow-derived mesenchymal stem cells rescue photoreceptor cells in the dystrophic retina of the rhodopsin knockout mouse
Transplantation of bone marrow-derived mesenchymal stem cells rescue photoreceptor cells in the dystrophic retina of the rhodopsin knockout mouse
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DOI：
10.1007/s00417-006-0382-7
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发表时间：
2007-03-01
影响因子：
2.7
通讯作者：
Schraermeyer, U.
中科院分区：
文献类型：
--
作者：
Arnhold, S.;Absenger, Y.;Schraermeyer, U.
视网膜色素变性是一种具有遗传背景的视网膜变性疾病。它涉及视网膜感光细胞的损失，因此周边视力。目前，对于这种疾病没有令人满意的治疗选择。就在最近，间充质干细胞的使用已经被讨论为视网膜变性的一种治疗选择，因为它们已经被证明可以分化成各种细胞类型，包括感光细胞。在这篇文章中，我们要调查的潜力间充质干细胞诱导救援作用的视网膜色素变性的动物模型，视紫红质基因敲除mouse.Methods的实验，三个实验组，每组10只动物。第一组由未处理的视紫红质敲除（rho（-/-））动物组成，用作对照。第二组由rho（-/-）小鼠组成，这些小鼠接受了小鼠间充质干细胞的注射，在移植前使用含有绿色荧光蛋白（GFP）序列的腺病毒载体进行转导。在第三假手术组中，动物仅接受培养基注射。移植后35天，GFP表达细胞检测到的视网膜以及在冷冻切片的整装制剂。为了检测挽救效果，制备了来自所有实验组的眼睛的半薄切片。结果组织学分析显示，移植后细胞不仅形态学上整合到视网膜色素上皮中，而且整合到神经视网膜的各层中，表现出神经元和胶质细胞的形态学特征。此外，显着的救援效果，所表现出的发生保存的感光细胞，detected.Conclusions我们的数据表明，间充质干细胞可以延长感光细胞的生存在视紫红质基因敲除小鼠，也提供了证据，在视网膜色素变性的治疗效益。
Background Retinitis pigmentosa belongs to a large group of degenerative diseases of the retina with a hereditary background. It involves loss of retinal photoreceptor cells and consequently peripheral vision. At present there are no satisfactory therapeutic options for this disease. Just recently the use of mesenchymal stem cells has been discussed as one therapeutical option for retinal degeneration, as they have been shown to differentiate into various cell types, including photoreceptor cells. In this article we wanted to investigate the potency of mesenchymal stem cells to induce rescue effects in an animal model for retinitis pigmentosa, the rhodopsin knockout mouse.Methods For the experiments, three experimental groups of 10 animals each were formed. The first group consisted of untreated rhodopsin knockout (rho(-/-)) animals used as controls. The second group consisted of rho(-/-) mice that had received an injection of mouse mesenchymal stem cells, which were transduced using an adenoviral vector containing the sequence for the green fluorescent protein (GFP) prior to transplantation. In the third sham group, animals received an injection of medium only. Thirty-five days after transplantation, GFP-expressing cells were detected in whole-mount preparations of the retinas as well as in cryostat sections. For the detection of rescue effects, semi-thin sections of eyes derived from all experimental groups were produced. Furthermore, rescue effects were also analysed ultrastructurally in ultrathin sections.Results Histological analysis revealed that after transplantation, cells morphologically integrated not only into the retinal pigment epithelium but also into layers of the neuroretina displaying neuronal and glial morphologies. Furthermore, significant rescue effects, as demonstrated by the occurrence of preserved photoreceptor cells, were detected.Conclusions Our data indicate that mesenchymal stem cells can prolong photoreceptor survival in the rhodopsin knockout mouse, also providing evidence of a therapeutical benefit in retinitis pigmentosa.