Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors.
Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors.
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DOI：
10.1016/j.stemcr.2017.11.001
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发表时间：
2018-01-09
影响因子：
5.9
通讯作者：
Swaroop A
中科院分区：
文献类型：
--
作者：
DiStefano T;Chen HY;Panebianco C;Kaya KD;Brooks MJ;Gieser L;Morgan NY;Pohida T;Swaroop A
多能干细胞可以分化成3D视网膜类器官，主要细胞类型会自我构图成极化的层状结构。在静态培养中，有机物的发育可能会受到氧气和营养物质扩散限制的阻碍。在这里，我们报告了一种使用旋转壁血管(RWV)生物反应器培养来自小鼠多能干细胞的视网膜器官的生物过程。RWV中的有机类物质表现出促进增殖、形态清晰和促进神经元分化的作用，包括神经节细胞和S视锥感受器。此外，RWV在第25天(D25)的类有机物显示出与D32在静态培养中相似的成熟和转录组特征，紧密地概括了出生后第6天小鼠视网膜在体内的时空发育。然而，有趣的是，视网膜类器官在这里测试的任何体外条件下都不会进一步分化，这表明功能成熟需要额外的条件。我们的研究表明，生物反应器可以加速和改善有机物的生长和分化，用于视网膜疾病的建模和治疗评估。利用生物反应器改善视网膜器官发生的优化生物反应器有机物培养中视网膜神经元的生长和分化更好地概述了生物反应器中视网膜的体内发育对额外因素的要求Swaroop及其同事在体外证明了旋转壁血管生物反应器培养为促进视网膜器官的生长和分化提供了有利的环境，紧密地概括了体内发育的早期阶段。
Pluripotent stem cells can be differentiated into 3D retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioprocess using rotating-wall vessel (RWV) bioreactors to culture retinal organoids derived from mouse pluripotent stem cells. Organoids in RWV demonstrate enhanced proliferation, with well-defined morphology and improved differentiation of neurons including ganglion cells and S-cone photoreceptors. Furthermore, RWV organoids at day 25 (D25) reveal similar maturation and transcriptome profile as those at D32 in static culture, closely recapitulating spatiotemporal development of postnatal day 6 mouse retina in vivo. Interestingly, however, retinal organoids do not differentiate further under any in vitro condition tested here, suggesting additional requirements for functional maturation. Our studies demonstrate that bioreactors can accelerate and improve organoid growth and differentiation for modeling retinal disease and evaluation of therapies. Optimization of improved retinal organogenesis using bioreactors Better growth and differentiation of retinal neurons in bioreactor organoid culture Recapitulation of in vivo retina development in bioreactor organoids Requirement of additional factors for functional maturation of the retina in vitro Swaroop and colleagues demonstrate that rotating-wall vessel bioreactor culture provides a favorable environment for improved growth and differentiation of retinal organoids, closely recapitulating early stages of development in vivo.
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影响因子：
14
作者：
Carpenedo, Richard L.;Bratt-Leal, Andrs M.;Marklein, Ross A.;Seaman, Scott A.;Bowen, Nathan J.;McDonald, John F.;McDevitt, Todd C.
通讯作者：
McDevitt, Todd C.
DOI：
10.1073/pnas.0508214103
发表时间：
2006-03-07
影响因子：
11.1
作者：
Akimoto, M;Cheng, H;Swaroop, A
通讯作者：
Swaroop, A
影响因子：
64.8
作者：
Eiraku, Mototsugu;Takata, Nozomu;Sasai, Yoshiki
通讯作者：
Sasai, Yoshiki
影响因子：
7.2
作者：
Heavner, Whitney;Pevny, Larysa
通讯作者：
Pevny, Larysa
影响因子：
9.7
作者：
Hunt, Nicola C.;Hallam, Dean;Lako, Majlinda
通讯作者：
Lako, Majlinda