A three-dimensional neural spheroid model for capillary-like network formation

Boutin, Molly E.; Kramer, Liana; Livi, Liane L.; Brown, Tyler; Moore, Christopher I.; Hoffman–Kim, Diane

doi:10.1016/j.jneumeth.2017.01.014

Cited by 45 publications

(50 citation statements)

References 49 publications

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“…Interestingly, recent 3D models not only show presence of neuronal and glial cell types but also the presence of endothelial cells. 146 Therefore, capillary-like networks in neural cultures containing developing OLs may aid the study of blood-derived factors on myelination. Because 3D cultures have complex interactions with the cellular and extracellular microenvironment that resemble important aspects of the in vivo situation, these are interesting tools in the study of microenvironmental factors.…”

Section: Future Of New Stem Cell Technologiesmentioning

confidence: 99%

The Healthy and Diseased Microenvironments Regulate Oligodendrocyte Properties

Leferink

Heine

2018

The American Journal of Pathology

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White matter disorders are characterized by deficient myelin or myelin loss, lead to a range of neurologic dysfunctions, and can result in early death. Oligodendrocytes, which are responsible for white matter formation, are the first targets for treatment. However, many studies indicate that failure of white matter repair goes beyond the intrinsic incapacity of oligodendrocytes to (re)generate myelin and that failed interactions with neighboring cells or factors in the diseased microenvironment can underlie white matter defects. Moreover, most of the white matter disorders show specific white matter pathology caused by different disease mechanisms. Herein, we review the factors within the cellular and the extracellular microenvironment regulating oligodendrocyte properties and discuss stem cell tools to identify microenvironmental factors of importance to the development of improved regenerative medicine for patients with white matter disorders.

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Section: Future Of New Stem Cell Technologiesmentioning

confidence: 99%

The Healthy and Diseased Microenvironments Regulate Oligodendrocyte Properties

Leferink

Heine

2018

The American Journal of Pathology

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“…Following on from this study, Boutin et al assessed the potential of this heterogeneous spheroid model to form capillary-like networks, the later playing an important role in protecting the neuronal environment. [42] Immunohistochemical analysis revealed that within 3 days, cortical endothelial cells seemed to form networks in the spheroids, which were surrounded by basement membrane components and relevant cell types. In future studies, this relatively simple model could offer valuable insights in understanding disorders linked to neurovascular dysfunction.…”

Section: Cell-self-assembly-based Approachesmentioning

confidence: 99%

“…Cell culture platforms: monolayer culture on conventional tissue culture substrates, single cell in 3D matrix, spheroid culture, and organoid culture. Obtained and modified from [42] with permission from Elsevier.…”

Section: Cell-self-assembly-based Approachesmentioning

confidence: 99%

Three-dimensional neuronal cell culture: in pursuit of novel treatments for neurodegenerative disease

et al. 2017

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To gain a better understanding of the underlying mechanisms of neurological disease, relevant tissue models are imperative. Over the years, this realization has fuelled the development of novel tools and platforms, which aim at capturing in vivo complexity. One example is the field of biofabrication, which focuses on fabrication of three-dimensional (3D) biologically functional products in a controlled and automated manner. Herein, we provide a general overview of classical 3D cell culture platforms, particularly in the context of neurodegenerative disease. Subsequently, the focus is put on bioprinting-based biofabrication, its potential to advance 3D neuronal cell culture and, to conclude, the relevant translational bottlenecks, which will need to be considered as the field evolves.

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“…The Clear T2 method has been widely described for spheroids clearing (Boutin & Hoffman-Kim, 2015;Boutin et al, 2018;Kabadi et al, 2015). Boutin and Hoffman-Kim (2015) used Clear T2 to process C6 glioma, primary cortical neuron, and NSC spheroids by embedding them during 10 min in 25/10% (v/w) formamide/PEG 8,000, followed (Cy3), β-III tubulin (Cy3), S100 (Cy3)) were detectable by CLSM at all depths within spheroids as well as the fine features within the center of the spheroids (Boutin & Hoffman-Kim, 2015).…”

Section: Clear T2mentioning

confidence: 99%

“…Recently, the same research group also showed the applicability of the Clear T2 method for the imaging of immunostained spheroids composed of primary-derived postnatal rodent cortex cells by CLSM and MPM, to study in vitro the formation of endothelial cell capillarylike structures (Boutin et al, 2018).…”

Section: Clear T2mentioning

confidence: 99%

Optical clearing methods: An overview of the techniques used for the imaging of 3D spheroids

Costa

Silva

Moreira

et al. 2019

Biotech & Bioengineering

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Spheroids have emerged as in vitro models that reproduce in a great extent the architectural microenvironment found in human tissues. However, the imaging of 3D cell cultures is highly challenging due to its high thickness, which results in a lightscattering phenomenon that limits light penetration. Therefore, several optical clearing methods, widely used in the imaging of animal tissues, have been recently explored to render spheroids with enhanced transparency. These methods are aimed to homogenize the microtissue refractive index (RI) and can be grouped into four different categories, namely (a) simple immersion in an aqueous solution with high RI;(b) delipidation and dehydration followed by RI matching; (c) delipidation and hyperhydration followed by RI matching; and (d) hydrogel embedding followed by delipidation and RI matching. In this review, the main optical clearing methods, their mechanism of action, advantages, and disadvantages are described. Furthermore, the practical examples of the optical clearing methods application for the imaging of 3D spheroids are highlighted. K E Y W O R D Simaging, light scattering, optical clearing, optical microscopy, spheroids.

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A three-dimensional neural spheroid model for capillary-like network formation

Cited by 45 publications

References 49 publications

The Healthy and Diseased Microenvironments Regulate Oligodendrocyte Properties

The Healthy and Diseased Microenvironments Regulate Oligodendrocyte Properties

Three-dimensional neuronal cell culture: in pursuit of novel treatments for neurodegenerative disease

Optical clearing methods: An overview of the techniques used for the imaging of 3D spheroids

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