Human induced pluripotent stem-derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized vascular endothelial growth factor secretion, and gene expression pattern similar to native RPE.
Human induced pluripotent stem-derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized vascular endothelial growth factor secretion, and gene expression pattern similar to native RPE.
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DOI：
10.1002/stem.635
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发表时间：
2011-05
期刊：
影响因子：
5.2
通讯作者：
Golestaneh, Nady
中科院分区：
文献类型：
--
作者：
Kokkinaki, Maria;Sahibzada, Niaz;Golestaneh, Nady
关键词：
老年性黄斑变性（AMD）是老年人失明的主要原因之一，并随着视网膜色素上皮（RPE）的死亡和光感受器变性而进展，从而导致中央视力受损。人类诱导多能干 (hiPS) 细胞的发现为使用患者特异性干细胞生成用于自体细胞治疗的组织和细胞治疗退行性疾病开辟了新途径。最近，RPE 细胞是从 hiPS 细胞产生的。然而，没有证据表明这些 hiPS 衍生的 RPE 具有完全区别于其他类型细胞的特定 RPE 功能。在这里，我们首次表明，在规定条件下由 hiPS 产生的 RPE 表现出与天然 RPE 相似的离子传输、膜电位、极化 VEGF 分泌和基因表达谱。因此，hiPS-RPE 可能是 AMD 中 RPE 替代疗法的一个非常好的候选者。然而，这些细胞表现出端粒快速缩短、DNA 染色体损伤和 p21 表达增加，导致细胞生长停滞。这种快速衰老可能会影响移植细胞在体内的存活，因此，只有非常早期的传代才应用于再生治疗。未来的研究需要集中于生成“安全”且可行的 hiPS 衍生体细胞。
Aged-related macular degeneration (AMD) is one of the major causes of blindness in aging population and progresses with death of retinal pigment epithelium (RPE) and photoreceptor degeneration inducing impairment of central vision. Discovery of human induced pluripotent stem (hiPS) cells has opened new avenues for the treatment of degenerative diseases using patient specific stem cells to generate tissues and cells for autologous cell-based therapy. Recently, RPE cells were generated from hiPS cells. However, there is no evidence that those hiPS-derived RPE possess specific RPE functions that fully distinguish them from other type of cells. Here we show for the first time that RPE generated from hiPS under defined conditions exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression profile similar to those of native RPE. The hiPS-RPE could therefore be a very good candidate for RPE replacement therapy in AMD. However, these cells show rapid telomere shortening, DNA chromosomal damage and increased p21 expression that cause cell growth arrest. This rapid senescence might affect the survival of the transplanted cells in vivo and therefore, only the very early passages should be used for regeneration therapies. Future research needs to focus on the generation of “safe” as well as viable hiPS-derived somatic cells.
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DOI：
10.1089/clo.2006.8.189
发表时间：
2006-09-01
期刊：
CLONING AND STEM CELLS
影响因子：
--
作者：
Lund, Raymond D.;Wang, Shaomei;Lanza, Robert
通讯作者：
Lanza, Robert
影响因子：
5.2
作者：
Lu, Bin;Malcuit, Christopher;Lund, Raymond
通讯作者：
Lund, Raymond
影响因子：
23.9
作者：
Marion, Rosa M.;Strati, Katerina;Blasco, Maria A.
通讯作者：
Blasco, Maria A.
DOI：
10.1073/pnas.0601990103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Lamba, Deepak A.;Karl, Mike O.;Reh, Thomas A.
通讯作者：
Reh, Thomas A.
影响因子：
4.4
作者：
Maminishkis, Arvydas;Chen, Shan;Miller, Sheldon S.
通讯作者：
Miller, Sheldon S.