Intercellular Adhesion-Dependent Cell Survival and ROCK-Regulated Actomyosin-Driven Forces Mediate Self-Formation of a Retinal Organoid

Lowe, Albert; Harris, Raven; Bhansali, Punita; Cvekl, Aleš; Liu, Wei

doi:10.1016/j.stemcr.2016.03.011

Cited by 88 publications

(102 citation statements)

References 38 publications

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“…The development of the intestinal organoid system in 2009 was a major technological advance for the stem cell organoids field. Since then, an extensive body of works have improved the methodology and expanded the range of tissue and organ types that can be investigated, such as brain, gastric intestine, liver, kidney, lung, pancreas, prostate, retina, cardic, blood vessel, and mammary gland . Their versatile nature and potential to generate human tissues endow organoids with a variety of applications.…”

Section: Hydrogels In Organoids Formationmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

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Section: Hydrogels In Organoids Formationmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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“…Some differences between mouse and human ESC-derived organoids were observed (Nakano et al, 2012). All of this appeared to occur without external forces and with apparently no input from the surrounding basal lamina (Lowe et al, 2016). Similarly, Pin et al (2015) investigated crypt fission by modeling intestinal organoids as a viscoelastic monolayer of incompressible cells that deform into a bud above a threshold.…”

Section: Models With No Gridmentioning

confidence: 99%

The physics of organoids: a biophysical approach to understanding organogenesis

Dahl-Jensen

Grapin-Botton

2017

Development

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Organoids representing a diversity of tissues have recently been created, bridging the gap between cell culture and experiments performed in vivo. Being small and amenable to continuous monitoring, they offer the opportunity to scrutinize the dynamics of organ development, including the exciting prospect of observing aspects of human embryo development live. From a physicist's perspective, their ability to self-organize -to differentiate and organize cells in space -calls for the identification of the simple rules that underlie this capacity. Organoids provide tractable conditions to investigate the effects of the growth environment, including its molecular composition and mechanical properties, along with the initial conditions such as cell number and type(s). From a theoretical standpoint, different types of in silico modeling can complement the measurements performed in organoids to understand the role of chemical diffusion, contact signaling, differential cell adhesion and mechanical controls. Here, we discuss what it means to take a biophysical approach to understanding organogenesis in vitro and how we might expect such approaches to develop in the future.

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“…The capacity to generate bona fide fetal-stage neural retinal cell types and tissues from human embryonic and induced pluripotent stem cells (hESCs and hiPSCs; collectively, hPSCs) has spurred their use in disease modeling (Tucker et al, 2011(Tucker et al, , 2013Jin et al, 2012;Phillips et al, 2014;Yoshida et al, 2015;Arno et al, 2016;Parfitt et al, 2016;Megaw et al, 2017;Schwarz et al, 2017;Sharma et al, 2017;Shimada et al, 2017;Deng et al, 2018) and photoreceptor (PR) replacement efforts (Lamba et al, 2009(Lamba et al, , 2010Hambright et al, 2012;Barnea-Cramer et al, 2016;Shirai et al, 2016;Chao et al, 2017;Gonzalez-Cordero et al, 2017;Mandai et al, 2017;Zhu et al, 2017Zhu et al, , 2018Iraha et al, 2018;Lakowski et al, 2018;McLelland et al, 2018;Gagliardi et al, 2018). Most of these studies employ hPSC differentiation methods that propagate retinal progeny as isolated 3D optic vesicle-like structures (OVs), also known as retinal organoids, in suspension culture (Meyer et al, 2009(Meyer et al, , 2011Nakano et al, 2012;Phillips et al, 2012Phillips et al, , 2018bSridhar et al, 2016;Reichman et al, 2014;Zhong et al, 2014;Kuwahara et al, 2015;Mellough et al, 2015;Singh et al, 2015;Lowe et al, 2016;…”

Section: Introductionmentioning

confidence: 99%

Reproducibility and staging of 3D human retinal organoids across multiple pluripotent stem cell lines

et al. 2018

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Numerous protocols have been described for producing neural retina from human pluripotent stem cells (hPSCs), many of which are based on the culture of 3D organoids. Although nearly all such methods yield at least partial segments of retinal structure with a mature appearance, variabilities exist within and between organoids that can change over a protracted time course of differentiation. Adding to this complexity are potential differences in the composition and configuration of retinal organoids when viewed across multiple differentiations and hPSC lines. In an effort to understand better the current capabilities and limitations of these cultures, we generated retinal organoids from 16 hPSC lines and monitored their appearance and structural organization over time by light microscopy, immunocytochemistry, metabolic imaging and electron microscopy. We also employed optical coherence tomography and 3D imaging techniques to assess and compare whole or broad regions of organoids to avoid selection bias. Results from this study led to the development of a practical staging system to reduce inconsistencies in retinal organoid cultures and increase rigor when utilizing them in developmental studies, disease modeling and transplantation.

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Intercellular Adhesion-Dependent Cell Survival and ROCK-Regulated Actomyosin-Driven Forces Mediate Self-Formation of a Retinal Organoid

Cited by 88 publications

References 38 publications

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

The physics of organoids: a biophysical approach to understanding organogenesis

Reproducibility and staging of 3D human retinal organoids across multiple pluripotent stem cell lines

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