Incorporating microglia-like cells in human induced pluripotent stem cell-derived retinal organoids.
Incorporating microglia-like cells in human induced pluripotent stem cell-derived retinal organoids.
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DOI：
10.1111/jcmm.17670
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发表时间：
2023-02
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
小胶质细胞是视网膜中主要的常驻免疫细胞。它们调节神经元的存活和突触的修剪，使它们成为正常发育所必需的。损伤后，它们调节适应性反应，在病理条件下，它们可以触发神经退化，加剧疾病的影响。从人类诱导的多能干细胞(HiPSCs)中提取的视网膜类有机物越来越多地被用于一系列应用，包括疾病模型、新疗法的开发和视网膜发生的研究。尽管视网膜与体内发育的视网膜有许多相似之处，但它们缺乏一些关键的生理功能，包括免疫细胞。我们设计了一种含有视网膜器质和小胶质细胞样(IMG)细胞的HiPSC共培养系统，并测试了它们的视网膜侵袭能力和功能。我们在13 周时将img掺入视网膜器质中，并在分化后15周和22 周测试它们对功能和发育的影响。我们的主要发现表明，IMG细胞能够在单一培养和与有机物质共培养时对内毒素攻击做出反应。我们表明，视网膜类器官发育正常，并保持了对光产生尖峰活动的能力。因此，这种新的体外共培养免疫活性视网膜模型提供了一个与体内人类视网膜更具相关性的平台。
Microglia are the primary resident immune cells in the retina. They regulate neuronal survival and synaptic pruning making them essential for normal development. Following injury, they mediate adaptive responses and under pathological conditions they can trigger neurodegeneration exacerbating the effect of a disease. Retinal organoids derived from human induced pluripotent stem cells (hiPSCs) are increasingly being used for a range of applications, including disease modelling, development of new therapies and in the study of retinogenesis. Despite many similarities to the retinas developed in vivo, they lack some key physiological features, including immune cells. We engineered an hiPSC co‐culture system containing retinal organoids and microglia‐like (iMG) cells and tested their retinal invasion capacity and function. We incorporated iMG into retinal organoids at 13 weeks and tested their effect on function and development at 15 and 22 weeks of differentiation. Our key findings showed that iMG cells were able to respond to endotoxin challenge in monocultures and when co‐cultured with the organoids. We show that retinal organoids developed normally and retained their ability to generate spiking activity in response to light. Thus, this new co‐culture immunocompetent in vitro retinal model provides a platform with greater relevance to the in vivo human retina.
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影响因子：
16.2
作者：
Lin YT;Seo J;Gao F;Feldman HM;Wen HL;Penney J;Cam HP;Gjoneska E;Raja WK;Cheng J;Rueda R;Kritskiy O;Abdurrob F;Peng Z;Milo B;Yu CJ;Elmsaouri S;Dey D;Ko T;Yankner BA;Tsai LH
通讯作者：
Tsai LH
DOI：
10.1016/j.bbrc.2012.03.139
发表时间：
2012-05-04
影响因子：
3.1
作者：
Huang T;Cui J;Li L;Hitchcock PF;Li Y
通讯作者：
Li Y
人类诱导的多能干细胞产生具有可变和养分依赖性效率的光响应性视网膜器官。
DOI：
10.1002/stem.2883
发表时间：
2018-10
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Hallam D;Hilgen G;Dorgau B;Zhu L;Yu M;Bojic S;Hewitt P;Schmitt M;Uteng M;Kustermann S;Steel D;Nicholds M;Thomas R;Treumann A;Porter A;Sernagor E;Armstrong L;Lako M
通讯作者：
Lako M
影响因子：
14
作者：
Dorgau, Birthe;Felemban, Majed;Lako, Majlinda
通讯作者：
Lako, Majlinda
影响因子：
5.9
作者：
Douvaras P;Sun B;Wang M;Kruglikov I;Lallos G;Zimmer M;Terrenoire C;Zhang B;Gandy S;Schadt E;Freytes DO;Noggle S;Fossati V
通讯作者：
Fossati V