Fate of Embryonic Stem Cell Derivatives Implanted into the Vitreous of a Slow Retinal Degenerative Mouse Model
Fate of Embryonic Stem Cell Derivatives Implanted into the Vitreous of a Slow Retinal Degenerative Mouse Model
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DOI：
10.1089/scd.2008.0057
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发表时间：
2009-03-01
影响因子：
4
通讯作者：
Trese, Michael T.
中科院分区：
文献类型：
--
作者：
Chaudhry, G. Rasul;Fecek, Christopher;Trese, Michael T.
干细胞疗法可能用于治疗视网膜变性和恢复视力。由于胚胎干细胞（ESCs）可以分化成几乎任何细胞类型，包括眼睛中发现的细胞类型，因此它们可以移植来修复或替换因遗传性疾病或创伤导致的受损或受伤的视网膜组织。在这项研究中，我们探讨了胚胎干细胞和胚胎干细胞衍生的神经祖细胞增殖和整合到rd12小鼠患病视网膜组织的潜力。这些rd12小鼠模仿了在人类中看到的缓慢和进行性视网膜变性。ESC和来自ESC的ESC衍生的神经祖细胞都存活并增殖，如黄色荧光蛋白荧光的增加所证明的。冷冻切片的视网膜组织的定量分析最初揭示了ESC和神经祖细胞都分化成表达神经标志物的细胞。然而，ESC增殖是稳健的，并导致视网膜结构的破坏和最终形成畸胎瘤超过6周后植入。相反，神经祖细胞增殖缓慢，但进一步分化并整合到眼睛的视网膜层中。神经祖细胞的分化代表了各种视网膜细胞类型，从细胞特异性标志物包括Nestin，Olig1和胶质细胞酸性蛋白的表达来判断。这些结果表明，胚胎干细胞衍生的神经祖细胞可以存活，增殖，并在植入到实验小鼠的眼睛分化，并可能用于治疗退化或受损的视网膜组织的细胞疗法。
Stem cell therapy may be used potentially to treat retinal degeneration and restore vision. Since embryonic stem cells (ESCs) can differentiate into almost any cell types, including those found in the eye, they can be transplanted to repair or replace damaged or injured retinal tissue resulting from inherited diseases or traumas. In this investigation, we explored the potential of ESCs and ESC-derived neuroprogenitors to proliferate and integrate into the diseased retinal tissue of rd12 mice. These rd12 mice mimic the slow and progressive retinal degeneration seen in humans. Both ESCs and ESC-derived neuroprogenitors from ESCs survived and proliferated as evidenced from an increase in yellow fluorescent protein fluorescence. Quantification analysis of cryosectioned retinal tissue initially revealed that both ESCs and neuroprogenitors differentiated into cells expressing neural markers. However, ESC proliferation was robust and resulted in the disruption of the retinal structure and the eventual formation of teratomas beyond 6 weeks postimplantation. In contrast, the neuroprogenitors proliferated slowly, but differentiated further and integrated into the retinal layers of the eye. The differentiation of neuroprogenitors represented various retinal cell types, as judged from the expression of cell-specific markers including Nestin, Olig1, and glial fibrillary acidic protein. These results suggest that ESC-derived neuroprogenitors can survive, proliferate, and differentiate when implanted into the eyes of experimental mice and may be used potentially as cell therapy for treating degenerated or damaged retinal tissue.