Outer segment formation of transplanted photoreceptor precursor cells.
Outer segment formation of transplanted photoreceptor precursor cells.
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移植的感光前体细胞的外节形成。
DOI：
10.1371/journal.pone.0046305
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ader M
中科院分区：
文献类型：
--
作者：
Eberle D;Kurth T;Santos-Ferreira T;Wilson J;Corbeil D;Ader M
光感受器前体细胞（PPC）移植到视网膜中代表了以光感受器损失为特征的致盲疾病的细胞替代的有希望的治疗。在临床前研究中，我们和其他人证明了移植的PPC整合到宿主外核层（ONL）并发育成成熟的光感受器。然而，光检测光感受器的一个关键特征，具有天然对齐的椎间盘膜斯台普斯的外段（OS），在移植后尚未详细研究。因此，我们使用从新生双转基因报告小鼠分离的PPC作为供体细胞，其中OS被绿色荧光蛋白选择性标记，而细胞体被红色荧光蛋白突出显示。使用基于CD73的磁性相关细胞分选富集PPC，随后将其移植到成年野生型或常染色体显性视网膜变性小鼠模型中。移植后三周，基于荧光报告基因表达鉴定供体光感受器，并在光学和电子显微镜水平监测OS形成。适当整合到宿主野生型视网膜中的供体细胞发展出OS，形成连接纤毛和良好对齐的盘膜斯台普斯类似于宿主周围的天然细胞。令人惊讶的是，大多数保留在视网膜下空间的未整合PPC也在野生型小鼠和受视网膜变性影响的小鼠中产生天然样OS。此外，与位于玻璃体侧的供体细胞相比，它们显示出改善的光感受器成熟和OS形成，这表明环境因素影响PPC分化和成熟。我们的结论是，移植的PPC，无论是否整合到主机ONL，能够产生有效的光检测，在野生型以及退化的视网膜中观察到的现象的细胞结构。鉴于患有视网膜色素变性的患者几乎失去了所有的光感受器，我们的发现对于开发基于细胞的疗法至关重要。
Transplantation of photoreceptor precursor cells (PPCs) into the retina represents a promising treatment for cell replacement in blinding diseases characterized by photoreceptor loss. In preclinical studies, we and others demonstrated that grafted PPCs integrate into the host outer nuclear layer (ONL) and develop into mature photoreceptors. However, a key feature of light detecting photoreceptors, the outer segment (OS) with natively aligned disc membrane staples, has not been studied in detail following transplantation. Therefore, we used as donor cells PPCs isolated from neonatal double transgenic reporter mice in which OSs are selectively labeled by green fluorescent protein while cell bodies are highlighted by red fluorescent protein. PPCs were enriched using CD73-based magnetic associated cell sorting and subsequently transplanted into either adult wild-type or a model of autosomal-dominant retinal degeneration mice. Three weeks post-transplantation, donor photoreceptors were identified based on fluorescent-reporter expression and OS formation was monitored at light and electron microscopy levels. Donor cells that properly integrated into the host wild-type retina developed OSs with the formation of a connecting cilium and well-aligned disc membrane staples similar to the surrounding native cells of the host. Surprisingly, the majority of not-integrated PPCs that remained in the sub-retinal space also generated native-like OSs in wild-type mice and those affected by retinal degeneration. Moreover, they showed an improved photoreceptor maturation and OS formation by comparison to donor cells located on the vitreous side suggesting that environmental cues influence the PPC differentiation and maturation. We conclude that transplanted PPCs, whether integrated or not into the host ONL, are able to generate the cellular structure for effective light detection, a phenomenon observed in wild-type as well as in degenerated retinas. Given that patients suffering from retinitis pigmentosa lose almost all photoreceptors, our findings are of utmost importance for the development of cell-based therapies.
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DOI：
10.1073/pnas.0401596101
发表时间：
2004-11-02
影响因子：
11.1
作者：
Coles, BLK;Angénieux, B;van der Kooy, D
通讯作者：
van der Kooy, D
影响因子：
4.4
作者：
Klassen, HJ;Ng, TF;Young, MJ
通讯作者：
Young, MJ
影响因子：
2
作者：
Lin, N;Fan, W;Turner, JE
通讯作者：
Turner, JE
DOI：
10.1073/pnas.97.22.11984
发表时间：
2000-10-24
影响因子：
11.1
作者：
Baird, GS;Zacharias, DA;Tsien, RY
通讯作者：
Tsien, RY
影响因子：
5.2
作者：
Merhi-Soussi, Faten;Angenieux, Brigitte;Arsenijevic, Yvan
通讯作者：
Arsenijevic, Yvan