High-throughput generation of spheroids using magnetic nanoparticles for three-dimensional cell culture

Kim, Jeong Ah; Choi, Jeewook; Kim, Min‐Soo; Rhee, Won Jong; Son, Boram; Jung, Hyun-Kyo; Park, Tai Hyun

doi:10.1016/j.biomaterials.2013.07.056

Cited by 83 publications

(90 citation statements)

References 30 publications

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“…This condition induces the geometry change of cell mass and promotes contact between cells, leading to cell aggregation. In addition, this system can facilitate multi-cellular co-culturing with agglomeration of different cell types [53,54].…”

Section: Magnetic Levitationmentioning

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: Magnetic Levitationmentioning

confidence: 99%

Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells

Ryu

Lee

Park

2019

Cells

335

270

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“…Microtissue fusion can also be achieved by magnetic force-driven tissue assembly [87]. By incorporating magnetic MPs into murine ESC aggregates, Bratt-Leal et al demonstrated facile manipulations of murine ESC aggregates, leading to fabrication of hybrid structures in an additive manner (Fig.…”

Section: Engineering 3d Microtissues and Organoids In Vitro: Levermentioning

confidence: 99%

On human pluripotent stem cell control: The rise of 3D bioengineering and mechanobiology

2015

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Human pluripotent stem cells (hPSCs) provide promising resources for regenerating tissues and organs and modeling development and diseases in vitro. To fulfill their promise, the fate, function, and organization of hPSCs need to be precisely regulated in a three-dimensional (3D) environment to mimic cellular structures and functions of native tissues and organs. In the past decade, innovations in 3D culture systems with functional biomaterials have enabled efficient and versatile control of hPSC fate at the cellular level. However, we are just at the beginning of bringing hPSC-based regeneration and development and disease modeling to the tissue and organ levels. In this review, we summarize existing bioengineered culture platforms for controlling hPSC fate and function by regulating inductive mechanical and biochemical cues coexisting in the synthetic cell microenvironment. We highlight recent excitements in developing 3D hPSC-based in vitro tissue and organ models with in vivo-like cellular structures, interactions, and functions. We further discuss an emerging multifaceted mechanotransductive signaling network – with transcriptional coactivators YAP and TAZ at the center stage – that regulate fates and behaviors of mammalian cells, including hPSCs. Future development of 3D biomaterial systems should incorporate dynamically modulated mechanical and chemical properties targeting specific intracellular signaling events leading to desirable hPSC fate patterning and functional tissue formation in 3D.

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“…However, experimental approaches based on cell-internalized magnetic nanoparticles have raised concerns regarding possible long-term toxic effects. To minimize the potential toxic effects of MNPs, several recent studies have suggested using MNPs isolated from magnetotactic bacteria [17], which are believed to be less toxic than chemically synthesized MNPs, fabrication of magnetoferritin nanoparticles, or construction of Janus magnetic cellular spheroids by concentrating nanoparticles in certain regions of spheroids, thus reducing MNPs-cell interactions [8]. Although effective, these approaches are rather complex and require time-consuming manipulation of cells or sophisticated methods of nanoparticle preparation.…”

Section: Introductionmentioning

confidence: 99%

Cell surface engineering with polyelectrolyte-stabilized magnetic nanoparticles: A facile approach for fabrication of artificial multicellular tissue-mimicking clusters

et al. 2015

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Regenerative medicine requires new ways to assemble and manipulate cells for fabrication of tissue-like constructs. Here we report a novel approach for cell surface engineering of human cells using polymer-stabilized magnetic nanoparticles (MNPs). Cationic polyelectrolyte-coated MNPs are directly deposited onto cellular membranes, producing a mesoporous semi-permeable layer and rendering cells magnetically responsive. Deposition of MNPs can be completed within minutes, under cell-friendly conditions (room temperature and physiologic media). Microscopy (TEM, SEM, AFM, and enhanced dark-field imaging) revealed the intercalation of nanoparticles into the cellular microvilli network. A detailed viability investigation was performed and suggested that MNPs do not inhibit membrane integrity, enzymatic activity, adhesion, proliferation, or cytoskeleton formation, and do not induce apoptosis in either cancer or primary cells. Finally, magnetically functionalized cells were employed to fabricate viable layered planar (two-cell layers) cell sheets and 3D multicellular spheroids.

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High-throughput generation of spheroids using magnetic nanoparticles for three-dimensional cell culture

Cited by 83 publications

References 30 publications

Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells

Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells

On human pluripotent stem cell control: The rise of 3D bioengineering and mechanobiology

Cell surface engineering with polyelectrolyte-stabilized magnetic nanoparticles: A facile approach for fabrication of artificial multicellular tissue-mimicking clusters

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