Microfluidic three-dimensional cell culture of stem cells for high-throughput analysis

Kim, Jeong Ah; Hong, Soohyun; Rhee, Won Jong

doi:10.4252/wjsc.v11.i10.803

Cited by 21 publications

(21 citation statements)

References 107 publications

(128 reference statements)

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“…The need for improved in vitro models has been widely recognized for screening approaches, such as those used in drug development and toxicology ( Frank et al, 2017 ; Bal-Price et al, 2018 ; Kim et al, 2019 ; Shafer et al, 2019 ). Drug development costs continue to rise, and it has long been reasoned that improved in vitro models of human physiology could lower these costs by improving preclinical studies and reducing failure rate of potential therapeutics in clinical trials ( Begley and Ellis, 2012 ).…”

Section: Brain Organoid Applicationsmentioning

confidence: 99%

“…Drug development costs continue to rise, and it has long been reasoned that improved in vitro models of human physiology could lower these costs by improving preclinical studies and reducing failure rate of potential therapeutics in clinical trials ( Begley and Ellis, 2012 ). Similarly, improved models would lead to increased detection sensitivity in toxicological screening assays, as these models would more accurately recapitulate physiology ( Bal-Price et al, 2018 ; Kim et al, 2019 ). While microphysiological systems (e.g., engineered microfluidic devices, described in detail in the next section) have improved in vitro models and offer precise control over culture parameters, organoids provide macroscale architecture and organization that is difficult to recreate in traditional 3D culture systems ( Bhatia and Ingber, 2014 ).…”

Section: Brain Organoid Applicationsmentioning

confidence: 99%

“…Advances in brain organoid complexity have come as a result of advances and new applications of various technologies. One such technology includes microfluidics, which allow for “organoids-on-a-chip” ( Wang et al, 2018 ; Kim et al, 2019 ; Park et al, 2019 ). Microfluidics have been used to control the cellular microenvironment and engineer organ-on-a-chip systems, which recapitulate specific physiological aspects of particular organs and tissues ( Bhatia and Ingber, 2014 ).…”

Section: Technological Advances For Brain Organoid Development and Chmentioning

confidence: 99%

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Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements

Passaro

Stice

2021

Front. Neurosci.

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Brain organoids, or cerebral organoids, have become widely used to study the human brain in vitro. As pluripotent stem cell-derived structures capable of self-organization and recapitulation of physiological cell types and architecture, brain organoids bridge the gap between relatively simple two-dimensional human cell cultures and non-human animal models. This allows for high complexity and physiological relevance in a controlled in vitro setting, opening the door for a variety of applications including development and disease modeling and high-throughput screening. While technologies such as single cell sequencing have led to significant advances in brain organoid characterization and understanding, improved functional analysis (especially electrophysiology) is needed to realize the full potential of brain organoids. In this review, we highlight key technologies for brain organoid development and characterization, then discuss current electrophysiological methods for brain organoid analysis. While electrophysiological approaches have improved rapidly for two-dimensional cultures, only in the past several years have advances been made to overcome limitations posed by the three-dimensionality of brain organoids. Here, we review major advances in electrophysiological technologies and analytical methods with a focus on advances with applicability for brain organoid analysis.

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Section: Brain Organoid Applicationsmentioning

confidence: 99%

Section: Brain Organoid Applicationsmentioning

confidence: 99%

Section: Technological Advances For Brain Organoid Development and Chmentioning

confidence: 99%

See 1 more Smart Citation

Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements

Passaro

Stice

2021

Front. Neurosci.

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“…The fate of cells in vivo is affected largely by the external microenvironment, including physical and chemical factors, cell-cell interaction, and cell-ECM interaction [47]. So, mimicking the real ECM is significant in the 3D HTBMS for cell cultures.…”

Section: The Microenvironment Construction Of 3d Htbms For Cell Culturementioning

confidence: 99%

The Fabrication and Application Mechanism of Microfluidic Systems for High Throughput Biomedical Screening: A Review

Song

et al. 2020

Micromachines

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Microfluidic systems have been widely explored based on microfluidic technology, and it has been widely used for biomedical screening. The key parts are the fabrication of the base scaffold, the construction of the matrix environment in the 3D system, and the application mechanism. In recent years, a variety of new materials have emerged, meanwhile, some new technologies have been developed. In this review, we highlight the properties of high throughput and the biomedical application of the microfluidic chip and focus on the recent progress of the fabrication and application mechanism. The emergence of various biocompatible materials has provided more available raw materials for microfluidic chips. The material is not confined to polydimethylsiloxane (PDMS) and the extracellular microenvironment is not limited by a natural matrix. The mechanism is also developed in diverse ways, including its special physical structure and external field effects, such as dielectrophoresis, magnetophoresis, and acoustophoresis. Furthermore, the cell/organ-based microfluidic system provides a new platform for drug screening due to imitating the anatomic and physiologic properties in vivo. Although microfluidic technology is currently mostly in the laboratory stage, it has great potential for commercial applications in the future.

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“…Microfluidic devices have very broad applications in biological assays from simple chemotaxis assays and it allowed to control the physiological relevance of the 3D culture by perfusion flow through micrometer size channels [14]. The culture systems can mimic cell-specific physiological conditions, like shear stressor chemical gradient [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

A Dynamic Hanging-Drop System for Mesenchymal Stem Cell Culture

Huang

Tzeng

Chen

et al. 2020

IJMS

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There have been many microfluid technologies combined with hanging-drop for cell culture gotten developed in the past decade. A common problem within these devices is that the cell suspension introduced at the central inlet could cause a number of cells in each microwell to not regularize. Also, the instability of droplets during the spheroid formation remains an unsolved ordeal. In this study, we designed a microfluidic-based hanging-drop culture system with the design of taper-tube that can increase the stability of droplets while enhancing the rate of liquid exchange. A ring is surrounding the taper-tube. The ring can hold the cells to enable us to seed an adequate amount of cells before perfusion. Moreover, during the period of cell culture, the mechanical force around the cell is relatively low to prevent stem cells from differentiate and maintain the phenotype. As a result of our hanging system design, cells are designed to accumulate at the bottom of the droplet. This method enhances convenience for observation activities and analysis of experiments. Thus, this microfluid chip can be used as an in vitro platform representing in vivo physiological conditions, and can be useful in regenerative therapy.

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Microfluidic three-dimensional cell culture of stem cells for high-throughput analysis

Cited by 21 publications

References 107 publications

Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements

Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements

The Fabrication and Application Mechanism of Microfluidic Systems for High Throughput Biomedical Screening: A Review

A Dynamic Hanging-Drop System for Mesenchymal Stem Cell Culture

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