Three-dimensional growth matrix for human embryonic stem cell-derived neuronal cells

Ylä‐Outinen, Laura; Joki, Tiina; Varjola, Mari; Skottman, Heli; Narkilahti, Susanna

doi:10.1002/term.1512

Cited by 41 publications

(65 citation statements)

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“…A 10% (w/w) sucrose solution in deionized water was used as a solvent for the hydrogel components to reduce osmotic pressure on the cells [5]. The GG solution was prepared at 5 mg/ml.…”

Section: Preparation Of Gg Hydrogelsmentioning

confidence: 99%

“…Hydrogel biomaterials can fulfill the biocompatibility (systemic scale) and cytocompatibility (cellular scale) requirements [8], and their tunable physical properties can mimic soft tissue, such as CNS [3][4][5]. Thus, while designing hydrogels for TE, important material characteristics to take into account are for example mechanical properties, porosity, permeability and transparency, especially for in vitro TE [4; 10-12].…”

Section: Introductionmentioning

confidence: 99%

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Bioamine-crosslinked gellan gum hydrogel for neural tissue engineering

et al. 2017

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Neural tissue engineering and three-dimensional in vitro tissue modeling require the development of biomaterials that take into account the specified requirements of human neural cells and tissue. In this study, an alternative method of producing biomimetic hydrogels based on gellan gum (GG) was developed by replacing traditional crosslinking methods with the bioamines spermidine and spermine. These bioamines were proven to function as crosslinkers for GG hydrogel at +37 °C, allowing for the encapsulation of human neurons. We studied the mechanical and rheological properties of the formed hydrogels, which showed biomimicking properties comparable to naïve rabbit brain tissue under physiologically relevant stress and strain. Human pluripotent stem cell-derived neuronal cells demonstrated good cytocompatibility in the GG-based hydrogels. Moreover, functionalization of GG hydrogels with laminin resulted in cell type-specific behavior: neuronal cell maturation and neurite migration.

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“…A 10% (w/w) sucrose solution in deionized water was used as a solvent for the hydrogel components to reduce osmotic pressure on the cells [5]. The GG solution was prepared at 5 mg/ml.…”

Section: Preparation Of Gg Hydrogelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bioamine-crosslinked gellan gum hydrogel for neural tissue engineering

et al. 2017

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“…However, so far there is far too few chemical testing data available to answer this question. One human ESC-based model has to be mentioned at this point which has been established for DNT testing purposes but has not been published with compounds yet -and thus was not recognized within this systematic review (Kapucu et al, 2012, Yla-Outinen et al, 2014. Differentiation of human ESC on multi electrode arrays (MEAs) was established within this work and neuronal network activities recorded.…”

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confidence: 99%

“…The 'Neuronal Network Endpoints' is data-wise the weakest, yet no promising system has been identified within these studies. Yet, as mentioned earlier, a promising human ESC-based model has been established for DNT testing purposes but has not been published with compounds yet -and thus was not recognized within this systematic review (Yla-Outinen et al, 2014, Kapucu et al, 2012. Differentiation of human ESC on multi electrode arrays (MEAs) was established within this work and neuronal network activities recorded.…”

mentioning

confidence: 99%

“…In this systematic review, only very few publications were identified measuring electrical network activity using rodent, mainly rat primary cells (record numbers 1901, 2021, 2319, 20775, 23876). However, although it seems that this important endpoint can also be measured with hESC-derived neuronal cultures (Kapucu et al, 2012, Yla-Outinen et al, 2014 it is necessary to establish standardized protocols for human-based network formation with NS/PC-based methods. Moreover, there is the urgent need to show that current human DNT compounds (Grandjean and Landrigan, 2014) are indeed able to disturb human network formation.…”

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confidence: 99%

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Literature review on in vitro and alternative Developmental Neurotoxicity (DNT) testing methods

Fritsche

Alm

Baumann

et al. 2015

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The goal of this systematic review performed under a contract with EFSA was the evaluation of information on assessment methods in the field of developmental neurotoxicity (DNT). Therefore, a systematic and comprehensive literature search and collection of scientific literature and all other relevant grey literature and website information (in English) from past 20 years until mid of April 2014 on the state of the art of in vivo DNT testing methods including novel and alternative non-mammalian models, in vitro test methods, in silico methods, read across and combination of testing methods in test batteries was performed. This systematic review identified a variety of methods covering early and later stages of neurodevelopment that have the ability to predict DNT of chemicals. Few in vivo models alternative to OECD TG 426 were identified. In general, the available published in vivo data is scattered and heterogeneous, making comparisons across exposure paradigms and compounds very difficult. Thus, to make more useful evaluations, publications with more consistent experimental designs are needed, and more focused in vivo-in vitro comparisons are needed to establish useful effect biomarkers and testing models. From the alternative methods, a testing strategy covering early and later neurodevelopmental stages (from stem cell to zebrafish larvae motor behaviour) can be assembled. For gaining regulatory acceptance, definition of biological application domains of alternative methods by performing e.g. in vitro -in vivo validation is needed. Moreover, protocols for cell-based and zebrafish assays need international standardization. With such standardized protocols, the test battery needs to be tested for its sensitivity and specificity by testing concentration-responses of known DNT positive and negative compounds across the different assays. Such data might then be used either for regulatory decision-making or compound prioritization in favour of a reduction of rodent guideline in vivo testing.

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Conducting Polymer Scaffolds for Hosting and Monitoring 3D Cell Culture

et al. 2017

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now clear that architectures that reproduce tissue organization in 3D are favored for studying function as first shown by Bissell and co-workers nearly 30 years ago. [5,6] Another emerging concept is the capacity for multiple cell types to auto-organize when given the appropriate mechanical cues. [7] A large variety of 3D models have been developed, with the major subtypes being spheroids/organoids, multilayered tissue like models, and scaffold models. [8] 3D tissues are frequently constructed as spheroids using hydrogel-like matrices such as Matrigel, [9] or PuraMatrix, [10] with a highly desirable degree of mechanical softness, however, there can be problems related to cost and inhomogeneity of the materials. [11] Multilayer models hold a lot of promise for applications such as skin toxicology measurements, [12] however, they cannot be easily applied for more complex tissue or organ constructs including vasculature. Considerable attention has thus focused on the development of biocompatible scaffold materials for hosting cells in 3D. A variety of synthetic and bio-derived polymers (some resorbable, some not) have been used to mimic the ECM or connective tissue. In terms of technology integration, the major advances so far for 3D cell biology have been related to materials and methods used for scaffold preparation, and integration of microfabrication techniques, for example for fluidics. As might be expected, a challenge of 3D culture over 2D is associated with the difficulty of oxygenation of tissues in the absence of vasculature. Microfluidics have gained favor for a number of reasons, including for perfusion, reduction in reagent volumes, and the fact that flow induced stress This work reports the design of a live-cell monitoring platform based on a macroporous scaffold of a conducting polymer, poly(3,4-ethylene dioxythiophene):poly(styrenesulfonate). The conducting polymer scaffolds support 3D cell cultures due to their biocompatibility and tissue-like elasticity, which can be manipulated by inclusion of biopolymers such as collagen. Integration of a media perfusion tube inside the scaffold enables homogenous cell spreading and fluid transport throughout the scaffold, ensuring long term cell viability. This also allows for co-culture of multiple cell types inside the scaffold. The inclusion of cells within the porous architecture affects the impedance of the electrically conducting polymer network and, thus, is utilized as an in situ tool to monitor cell growth. Therefore, while being an integral part of the 3D tissue, the conducting polymer is an active component, enhancing the tissue function, and forming the basis for a bioelectronic device with integrated sensing capability.

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Three-dimensional growth matrix for human embryonic stem cell-derived neuronal cells

Cited by 41 publications

References 46 publications

Bioamine-crosslinked gellan gum hydrogel for neural tissue engineering

Bioamine-crosslinked gellan gum hydrogel for neural tissue engineering

Literature review on in vitro and alternative Developmental Neurotoxicity (DNT) testing methods

Conducting Polymer Scaffolds for Hosting and Monitoring 3D Cell Culture

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