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Subretinal Transplantation of Human Amniotic Membrane Mesenchymal Stem Cell Restores Retinal Function Loss on Light-induced Retinopathy

視網膜下腔移植羊膜間質幹細胞可改善光照誘發之視網膜功能退化

摘要


Background and Purpose: Light-induced retinopathy is an animal model that mimics the photoreceptor apoptotic progress in retinal degeneration. This study examines the effects of human amniotic membrane mesenchymal stem cells (hAM-MSCs) on a light-induced animal model. Methods: Male Sprague-Dawley (SD) rats were exposed to 5000 to 7 000 lux for 7 d and treated with hAM-MSCs. The functional changes of the retinas were monitored by electroretinogram (ERG). Frozen retinal sections were analyzed for histology and immunohistochemistry. Results: Severe damages presented, including a large number of apoptotic cells on the ONL, a decrease in the ONL thickness, and the reduction of ERG following 7 d of light exposure. Retinal structure and function were recovered following treatment with hAM-MSCs, and the grafted hAM-MSCs were differentiated into retinal pigment epithelium cells (RPE), photoreceptors, and Müller cells. The transplantation of the hAM-MSCs improved the retinal function and morphology, and the hAM-MSCs differentiated into retinal cells. Conclusion: These findings show that hAM-MSCs may be possibly used to treat retinal degenerative diseases.

並列摘要


背景目的:以光照誘發視網膜退化病變的動物模式來探討視網膜感光細胞凋亡的變化,並探討視網膜下腔移植羊膜間質幹細胞可能的治療或視網膜保護功效。實驗方法:實驗以SD大鼠為實驗動物,飼養於光照照度5000到7000 lux,光暗循環各12小時的環境下7天,用以誘發視網膜退化動物模式。光照完成後,部分動物進行視網膜下腔移植人類羊膜間質幹細胞,另一部分動物同部位注射生理食鹽水作為對照組,並以視網膜電位圖、視網膜組織切片、以及免疫螢光染色等方式進行不同組別之研究。結果討論:實驗結果顯示,光照一周後視網膜感光細胞有明顯減少(凋亡)的現象,而視網膜電位圖亦顯示視網膜功能已經明顯退化。經過視網膜下腔移植人類羊膜間質幹細胞之後,三至五週後可以見到有標記的移植羊膜間質細胞已經嵌入被移殖動物的視網膜組之中,並且減少感光細胞的凋亡。這些接受移植的動物在視網膜電位圖的表現也比對照組顯示較佳的視網膜功能。藉由免疫螢光染色的技術更進一步發現,這些移植的羊膜間質幹細胞漸漸分化為視網膜的色素上皮細胞(RPE)、感光細胞(photoreceptor)、以及穆勒膠細胞(Müller cells)。結論:研究結果顯示移植人類間質幹細胞可以修復因長期光照造成受損的視網膜感光細胞並於光照後維持視網膜功能,期望研究成果期望可以做為臨床治療視網膜退化疾病之參考。

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