Function of human pluripotent stem cell-derived photoreceptor progenitors in blind mice.
Function of human pluripotent stem cell-derived photoreceptor progenitors in blind mice.
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DOI：
10.1038/srep29784
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发表时间：
2016-07-13
影响因子：
4.6
通讯作者：
Lanza R
中科院分区：
文献类型：
--
作者：
Barnea-Cramer AO;Wang W;Lu SJ;Singh MS;Luo C;Huo H;McClements ME;Barnard AR;MacLaren RE;Lanza R
视网膜色素变性（RP）引起的感光器变性是遗传性视网膜盲的主要原因。光感受器细胞替代可以通过恢复光敏细胞以形成将信息传递到下游视网膜层的连接来保持完全退化视网膜的修复潜力。这项研究评估了来自人胚胎和诱导多能干细胞（ESC和iPSC）的光感受器祖细胞的治疗潜力，使用适合未来临床试验的方案。ESC和iPSC在限定的条件下在四个特定阶段中培养，导致产生光感受器样祖细胞的近同质群体。在移植到患有终末期视网膜变性的小鼠中后，这些细胞分化成光感受器并形成与宿主视网膜神经元连接的细胞层。两项视觉行为测试证明，治疗组动物的视觉功能部分恢复。此外，功能改善的程度与移植细胞的数量呈正相关。使用ESC或iPSC作为源材料观察到类似的功效。这些数据验证了人多能干细胞用于视网膜疾病中光感受器再生的光感受器替代疗法的潜力。
Photoreceptor degeneration due to retinitis pigmentosa (RP) is a primary cause of inherited retinal blindness. Photoreceptor cell-replacement may hold the potential for repair in a completely degenerate retina by reinstating light sensitive cells to form connections that relay information to downstream retinal layers. This study assessed the therapeutic potential of photoreceptor progenitors derived from human embryonic and induced pluripotent stem cells (ESCs and iPSCs) using a protocol that is suitable for future clinical trials. ESCs and iPSCs were cultured in four specific stages under defined conditions, resulting in generation of a near-homogeneous population of photoreceptor-like progenitors. Following transplantation into mice with end-stage retinal degeneration, these cells differentiated into photoreceptors and formed a cell layer connected with host retinal neurons. Visual function was partially restored in treated animals, as evidenced by two visual behavioral tests. Furthermore, the magnitude of functional improvement was positively correlated with the number of engrafted cells. Similar efficacy was observed using either ESCs or iPSCs as source material. These data validate the potential of human pluripotent stem cells for photoreceptor replacement therapies aimed at photoreceptor regeneration in retinal disease.