Hydrogels with an embossed surface: An all-in-one platform for mass production and culture of human adipose-derived stem cell spheroids

Kim, Se-Jeong; Park, Jaesung; Byun, Hayeon; Park, Young Woo; Major, Luke G.; Lee, Dong Yun; Choi, Yu Suk; Shin, Heungsoo

doi:10.1016/j.biomaterials.2018.10.025

Cited by 61 publications

(58 citation statements)

References 59 publications

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“…By adjusting the physical properties of hydrogel materials, the size of a spheroid can be optimized. To control the size of spheroids, weak adhesive materials can be used and physically embossed patterns on the surface of the hydrogel should be fabricated [66]. In addition, another main property of a hydrogel is the capability to deliver cells directly.…”

Section: Particlesmentioning

confidence: 99%

Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells

Ryu

Lee

Park

2019

Cells

335

270

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Owing to the importance of stem cell culture systems in clinical applications, researchers have extensively studied them to optimize the culture conditions and increase efficiency of cell culture. A spheroid culture system provides a similar physicochemical environment in vivo by facilitating cell-cell and cell-matrix interaction to overcome the limitations of traditional monolayer cell culture. In suspension culture, aggregates of adjacent cells form a spheroid shape having wide utility in tumor and cancer research, therapeutic transplantation, drug screening, and clinical study, as well as organic culture. There are various spheroid culture methods such as hanging drop, gel embedding, magnetic levitation, and spinner culture. Lately, efforts are being made to apply the spheroid culture system to the study of drug delivery platforms and co-cultures, and to regulate differentiation and pluripotency. To study spheroid cell culture, various kinds of biomaterials are used as building forms of hydrogel, film, particle, and bead, depending upon the requirement. However, spheroid cell culture system has limitations such as hypoxia and necrosis in the spheroid core. In addition, studies should focus on methods to dissociate cells from spheroid into single cells.

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Section: Particlesmentioning

confidence: 99%

Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells

Ryu

Lee

Park

2019

Cells

335

270

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“…These microgels are crosslinked in stable oil shells containing various hydrogel precursors, such as alginate, agarose, GelMA, collagen, PEGDA, and PEGNB . Such hydrogels are also adapted to micromolding methods to produce defined microgels, like micro cuboids, for cell culture, aggregation and alignment . To precisely control the architectures of microgels in a high‐throughput manner, photopatterning are raised as a prior option.…”

Section: Snapshot Of Hydrogelsmentioning

confidence: 99%

“…Surface topographies have also been applied to regulate cell migration and alignment to form specific organoids. For example, Tetronic‐tyramine hydrogel substrate with an embossed surface was casted from a polydimethylsiloxane (PDMS) mold for massive production and culture of stem cell spheroids . Human adipose‐derived stem cells were easily aggregated into spheroids with uniform size on hydrogel's surface, which provided a versatile platform for standardized EBs generation or even organoids formation.…”

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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“…This is because the cells cultivated in 3D configuration are exposed to the milieu that is more similar to in vivo tissues compared to that grown in conventional 2D configuration (Oliveira et al, 2018). More specifically, 3D-cultured cells exhibit several in vivo-like characteristics in terms of the morphology, behavior, metabolism, cellular heterogeneity, and cell-to-cell or cell-to-matrix interactions, which are all diminished in the 2D-cultivated cells (Kuo et al, 2017;Oliveira et al, 2018;Kim et al, 2019). Therefore, cells cultured in 3D configuration and engineered to micro-scaled tissues represent a better in vitro model that recapitulates the physiological conditions of native tissues and has emerged as powerful tools for biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

Development of a Novel Hanging Drop Platform for Engineering Controllable 3D Microenvironments

Cho

Chiang

Hsieh

et al. 2020

Front. Cell Dev. Biol.

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Conventional biomedical research is mostly performed by utilizing a two-dimensional monolayer culture, which fails to recapitulate the three-dimensional (3D) organization and microenvironment of native tissues. To overcome this limitation, several methods are developed to fabricate microtissues with the desired 3D microenvironment. However, they tend to be time-consuming, labor-intensive, or costly, thus hindering the application of 3D microtissues as models in a wide variety of research fields. In the present study, we have developed a pressure-assisted network for droplet accumulation (PANDA) system, an easy-to-use chip that comprises a multichannel fluidic system and a hanging drop cell culture module for uniform 3D microtissue formation. This system can control the desired artificial niches for modulating the fate of the stem cells to form the different sizes of microtissue by adjusting the seeding density. Furthermore, a large number of highly consistent 3D glomerulus-like heterogeneous microtissues that are composed of kidney glomerular podocytes and mesenchymal stem cells have been formed successfully. These data suggest that the developed PANDA system can be employed as a rapid and economical platform to fabricate microtissues with tunable 3D microenvironment and cellular heterogeneity, thus can be employed as tissue-mimicking models in various biomedical research.

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Hydrogels with an embossed surface: An all-in-one platform for mass production and culture of human adipose-derived stem cell spheroids

Cited by 61 publications

References 59 publications

Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells

Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells

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

Development of a Novel Hanging Drop Platform for Engineering Controllable 3D Microenvironments

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