3D Engineering of Ocular Tissues for Disease Modeling and Drug Testing

Boutin, Molly E.; Hampton, Christopher; Quinn, R.; Ferrer, Marc; Song, Min Jae

doi:10.1007/978-3-030-28471-8_7

Cited by 15 publications

(13 citation statements)

References 108 publications

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“…Grenier et al (2020) mentioned in a diagram the perspective of generating a high-throughput platform for drug testing including image analysis on cleared cerebral organoids with deep learning to identify functional and architectural markers. The authors also discussed the challenges allowing integration of additional variables and risk factors (toxic agents, vasculature) in order to make cerebral organoids a formidable and scalable system to improve our understanding, provide precision to diagnostic and prognostic predictions and personalize drug discovery efforts for neurodegenerative diseases Of note, in another field, Boutin et al (2019) studied retinal organoids to summarize perspectives on drug testing. One of their expectations was also to apply machine learning on both high-content cell imaging and others chemical methods for their retinal model.…”

Section: Scope and Positioning Of This Reviewmentioning

confidence: 99%

Recent Trends and Perspectives in Cerebral Organoids Imaging and Analysis

Martin

Chane

Clouchoux³

et al. 2021

Front. Neurosci.

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Purpose: Since their first generation in 2013, the use of cerebral organoids has spread exponentially. Today, the amount of generated data is becoming challenging to analyze manually. This review aims to overview the current image acquisition methods and to subsequently identify the needs in image analysis tools for cerebral organoids.Methods: To address this question, we went through all recent articles published on the subject and annotated the protocols, acquisition methods, and algorithms used.Results: Over the investigated period of time, confocal microscopy and bright-field microscopy were the most used acquisition techniques. Cell counting, the most common task, is performed in 20% of the articles and area; around 12% of articles calculate morphological parameters. Image analysis on cerebral organoids is performed in majority using ImageJ software (around 52%) and Matlab language (4%). Treatments remain mostly semi-automatic. We highlight the limitations encountered in image analysis in the cerebral organoid field and suggest possible solutions and implementations to develop.Conclusions: In addition to providing an overview of cerebral organoids cultures and imaging, this work highlights the need to improve the existing image analysis methods for such images and the need for specific analysis tools. These solutions could specifically help to monitor the growth of future standardized cerebral organoids.

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Section: Scope and Positioning Of This Reviewmentioning

confidence: 99%

Recent Trends and Perspectives in Cerebral Organoids Imaging and Analysis

Martin

Chane

Clouchoux³

et al. 2021

Front. Neurosci.

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“…Apart from organoid technology, the development of innovative tools, including tissue engineering approaches and microfluidics, has marked a major step forward in 3D culture models with iPSC-derived RGCs [19]. Different biomaterials can be used to engineer artificial scaffolds, and the progress in microfabrication techniques generates the possibility of precisely controlling their biophysical and biochemical properties.…”

Section: Biomaterials-based Microfluidics To Improve Ipscs-derived Rgcs 3d Modelsmentioning

confidence: 99%

“…Moreover, iPSCs could be used in regenerative medicine through a variety of different approaches, including autologous therapies, the CRISPR/Cas9 system to edit genomic DNA at a precise locus in iPSCs or high-throughput drug screening assays [17,18]. Recently, 3D techniques have appeared, providing more accurate 3D cellular in vitro systems with the intent of faithfully recapitulating retinal development; these techniques include organoid technology and tissue engineering [19].…”

Section: Introductionmentioning

confidence: 99%

Hereditary Optic Neuropathies: Induced Pluripotent Stem Cell-Based 2D/3D Approaches

García-López

Arenas

Gallardo

2021

Genes

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Inherited optic neuropathies share visual impairment due to the degeneration of retinal ganglion cells (RGCs) as the hallmark of the disease. This group of genetic disorders are caused by mutations in nuclear genes or in the mitochondrial DNA (mtDNA). An impaired mitochondrial function is the underlying mechanism of these diseases. Currently, optic neuropathies lack an effective treatment, and the implementation of induced pluripotent stem cell (iPSC) technology would entail a huge step forward. The generation of iPSC-derived RGCs would allow faithfully modeling these disorders, and these RGCs would represent an appealing platform for drug screening as well, paving the way for a proper therapy. Here, we review the ongoing two-dimensional (2D) and three-dimensional (3D) approaches based on iPSCs and their applications, taking into account the more innovative technologies, which include tissue engineering or microfluidics.

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“…This heterogeneity and imprecision limit human RtOg procurement for preclinical trials 26 and in vitro investigations. Many approaches, including bioreactors [28][29][30][31][32][33][34] and optimized production protocols 26,35 are investigated to standardize RtOg production and maintenance over months. Controlled and predictable RtOg production is important to ensure a quality-controlled tissue product that is suitable for transplantation.…”

Section: Introductionmentioning

confidence: 99%

Retinal Organoids On-a-Chip: A 3D Printed Micro-Millifluidic Bioreactor for Long-Term Retinal Organoid Maintenance

Xue¹,

Seiler²,

Tang³

et al. 2021

Preprint

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<div>Retinal degeneration is a leading cause of vision impairment and blindness worldwide and medical care for advanced disease does not exist. Stem cell-derived retinal organoids (RtOgs) became an emerging tool for tissue replacement therapy. However, existing RtOg production methods are highly heterogeneous. Controlled and predictable methodology and tools are needed to standardize RtOg production and maintenance. In this study, we designed a shear stress-free micro-millifluidic bioreactor. We used a stereolithography (SLA) 3D printer to fabricate a mold from which Polydimethylsiloxane (PDMS) was cast. The multi-chamber bioreactor design and fabrications methods easily combined micro and millimeter features with very low cost and short manufacturing time. We optimized the chip design using in silico simulations and in vitro evaluation to optimize mass transfer efficiency and concentration uniformity in each culture chamber. We successfully cultured RtOgs on an optimized bioreactor chip for 37 days. We also characterized the RtOgs produced by static dish culture and chip culture methods using qualitative and quantitative techniques. Phase contrast imaging showed that both conventional and chip-cultured RtOgs developed a transparent outermost surface structure. Fluorescence lifetime imaging (FLIM) showed that RtOgs on the chip had significantly lower long lifetime species (LLS) ratio than static cultured ones, which demonstrated that bioreactor cultured RtOgs exhibited less oxidative stress. RtOgs in bioreactor culture demonstrated higher NADH signal overall, but both bioreactor and conventional cultures showed similar free/bound NADH ratio over time, which indicated normal differentiation time course. RtOg gene expression was examined by fluorescence imaging and quantitative polymerase chain reaction (qPCR) analyses. RtOgs in both groups showed thick nuclear outer layers expressing CRX on day 120 of differentiation. The gene profiling showed both groups expressed retinal progenitor genes and most of the tested photoreceptor markers. We, therefore, validated an autonomous micro-millifluidic device with significantly reduced shear stress and lower oxidative stress to produce RtOgs of equal or greater quality than those maintained in conventional static culture. </div>

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3D Engineering of Ocular Tissues for Disease Modeling and Drug Testing

Cited by 15 publications

References 108 publications

Recent Trends and Perspectives in Cerebral Organoids Imaging and Analysis

Recent Trends and Perspectives in Cerebral Organoids Imaging and Analysis

Hereditary Optic Neuropathies: Induced Pluripotent Stem Cell-Based 2D/3D Approaches

Retinal Organoids On-a-Chip: A 3D Printed Micro-Millifluidic Bioreactor for Long-Term Retinal Organoid Maintenance

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