Retinal incorporation and differentiation of mesenchymal stem cells intravitreally injected in the injured retina of rats
Retinal incorporation and differentiation of mesenchymal stem cells intravitreally injected in the injured retina of rats
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DOI：
10.1590/s0004-27492008000500007
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发表时间：
2008-10-01
影响因子：
1
通讯作者：
Goes, Alfredo Miranda
中科院分区：
文献类型：
--
作者：
Castanheira, Paula;Torquetti, Leonardo;Goes, Alfredo Miranda
目的：目的：观察间充质干细胞（MSCs）在视网膜损伤大鼠玻璃体腔内的整合和分化情况。方法：成年大鼠视网膜激光损伤后移植DAPI标记的BM-MSCs移植物。为了评估BM-MSC在激光损伤的视网膜中的整合和分化，在损伤/移植后2.4周和8周评价宿主视网膜。结果如下：我们的结果表明，移植的细胞在视网膜中存活至少8周，几乎所有的BM-MSCs迁移和整合到神经视网膜，特别是在外核层（ONL），内核层（INL）和神经节细胞层（GCL），而一个子集的移植细胞被发现在视网膜下腔移植后。在8周时，用几种视网膜特异性标记物进行的免疫组织化学分析显示，大多数移植细胞表达视紫红质（一种视杆细胞标记物），其次是小白蛋白（一种双极细胞和无长突细胞的标记物）。少数细胞亚群能够表达神经胶质标志物，神经胶质酸性蛋白。然而，移植细胞未能表达泛细胞角蛋白，视网膜色素上皮标记。结论：骨髓间充质干细胞具有向视网膜神经元分化的潜能。总之，这些发现可能与未来的视网膜变性修复间充质干细胞治疗研究具有临床相关性。
Purpose: To evaluate the pattern of retinal integration and differentiation of mesenchymal stem cells (MSCs) injected into the vitreous cavity of rat eyes with retinal injury. Methods: Adult rat retinas were submitted to laser damage followed by transplantation of DAPI-labeled BM-MSCs grafts. To assess the integration and differentiation of BM-MSCs in laser-injured retina, host retinas were evaluated 2.4 and 8 weeks after injury/transplantation. Results: Our results demonstrated that the grafted cells survived in the retina for at least 8 weeks and almost all BM-MSCs migrated and incorporated into the neural retina, specifically in the outer nuclear layer (ONL), inner nuclear layer (INL) and ganglion cell layer (GCL) while a subset of grafted cells were found in the subretinal space posttransplantation. At 8 weeks immunohistochemical analysis with several retinal specific markers revealed that the majority of the grafted cells expressed rhodopsin, a rod photoreceptor marker, followed by parvalbumin, a marker for bipolar and amacrine cells. A few subsets of cells were able to express a glial marker, glial fibrillary acidic protein. However, grafted cells failed to express pan-cytokeratin, a retinal pigment epithelium marker. Conclusions: These results suggest the potential of BM-MSCs to differentiate into retinal neurons. Taken together, these findings might be clinically relevant for future mesenchymal stem cell therapy studies concerning retinal degeneration repair.