3D culture models of tissues under tension

Eyckmans, Jeroen; Chen, Christopher

doi:10.1242/jcs.198630

Cited by 48 publications

(45 citation statements)

References 110 publications

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“…This non-integrated matrix could be viewed as an inefficiency of the microtissue model to retain all matrix produced in a continuous tissue mass. Because BMSC do not divide markedly in 3D microtissue cultures, possibly due to the lack of cell tension normally provided by stiff 2D tissue culture plastic (Eyckmans and Chen 2017), replenishing or maintaining a viable cell pool may also be compromised in this system.…”

Section: Discussionmentioning

confidence: 99%

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Bone marrow-derived stem/stromal cells (BMSC) 3D microtissues cultured in BMP-2 supplemented osteogenic induction medium are prone to adipogenesis

et al. 2018

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Bone marrow-derived mesenchymal stem/stromal cells (BMSC) may facilitate bone repair through secretion of factors that stimulate endogenous repair processes or through direct contribution to new bone through differentiation into osteoblast-like cells. BMSC microtissue culture and differentiation has been widely explored recently, with high-throughput platforms making large-scale manufacture of microtissues increasingly feasible. Bone-like BMSC microtissues could offer an elegant method to enhance bone repair, especially in small-volume non-union defects, where small diameter microtissues could be delivered orthoscopically. Using a high-throughput microwell platform, our data demonstrate that (1) BMSC in 3D microtissue culture result in tissue compaction, rather than growth, (2) not all mineralised bone-like matrix is incorporated in the bulk microtissue mass and (3) a significant amount of lipid vacuole formation is observed in BMSC microtissues exposed to BMP-2. These factors should be considered when optimising BMSC osteogenesis in microtissues or developing BMSC microtissue-based therapeutic delivery processes.

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Section: Discussionmentioning

confidence: 99%

“…The prevalence of lipid vacuoles increased in osteogenic medium + BMP-2 relative to maintenance medium. Scale bars = 100 μm is reduced (Eyckmans and Chen 2017) and this may limit the biological capacity of BMSC to generate or retain significant amounts of bone-like matrix in microtissue culture.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow-derived stem/stromal cells (BMSC) 3D microtissues cultured in BMP-2 supplemented osteogenic induction medium are prone to adipogenesis

et al. 2018

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“…Mechanical forces mediate this process in addition to 3D migration of immune cells through tissues. Improvements in 3D culture models are providing more physiologic tools that accurately depict the in vivo mechanics of cell migration through vessel walls and throughout tissues . The force‐dependent mechanisms governing 3D leukocyte migration are complex, because vascular endothelial cells are also mechanosensitive .…”

Section: Mechanical Force In the Service Of Leukocyte Functionmentioning

confidence: 99%

“…Furthermore, this work sheds light onto how cytoskeletal alterations due to environmental changes act upon signaling molecules to shape immune cell output. This study compared the effects of collagen coated 2D wells to 3D collagen matrices in T‐cell migration, emphasizing how 2D systems may not be optimal for delineation of mechanosensitive mechanisms, and implementation of 3D systems more accurately depicts these processes in migrating leukocytes …”

Section: Mechanical Force In the Service Of Leukocyte Functionmentioning

confidence: 99%

“…Improvements in 3D culture models are providing more physiologic tools that accurately depict the in vivo mechanics of cell migration through vessel walls and throughout tissues. 61 The force-dependent mechanisms governing 3D leukocyte migration are complex, because vascular endothelial cells are also mechanosensitive. 13,[62][63][64] A recent study decoupled forces exerted by leukocytes and vascular endothelial cells in order to elucidate the function of each cell type during lymphocyte diapedesis.…”

Section: Force In the Regulation Of Leukocyte Rolling And Diapedesismentioning

confidence: 99%

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Lymphocyte mechanotransduction: The regulatory role of cytoskeletal dynamics in signaling cascades and effector functions

Ben‐Shmuel¹,

Joseph²,

Sabag³

et al. 2019

Journal of Leukocyte Biology

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The process of mechanotransduction, that is, conversion of physical forces into biochemical signaling cascades, has attracted interest as a potential mechanism for regulating immune cell activation. The cytoskeleton serves a critical role in a variety of lymphocyte functions, from cellular activation, proliferation, adhesion, and migration, to creation of stable immune synapses, and execution of functions such as directed cytotoxicity. Though traditionally considered a scaffold that enables formation of signaling complexes that maintain stable immune synapses, the cytoskeleton was additionally shown to play a dynamic role in lymphocyte signaling cascades by sensing physical cues such as substrate rigidity, and transducing these mechanical features into chemical signals that ultimately influence lymphocyte effector functions. It is thus becoming clear that cytoskeletal dynamics are essential for the lymphocyte response, beyond the role of the cytoskeleton as a stationary framework. Here, we describe the transduction of extracellular forces to activate signaling pathways and effector functions mediated through the cytoskeleton in lymphocytes. We also highlight recent discoveries of cytoskeleton‐mediated mechanotransduction on intracellular signaling pathways in NK cells.

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Electron Microscopy for 3D Scaffolds–Cell Biointerface Characterization

et al. 2018

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Cell fate is largely determined by interactions that occur at the interface between cells and their surrounding microenvironment. For this reason, especially in the field of tissue‐engineering, there is a growing interest in developing techniques that allow evaluating cell–material interaction at the nanoscale, particularly focusing on cell adhesion processes. While for 2D culturing systems a consolidated series of tools already satisfy this need, in 3D environments, more closely recapitulating complex in vivo structures, there is still a lack of procedures furthering the comprehension of cell–material interactions. Here, the use of scanning electron microscopy coupled with a focused ion beam (SEM/FIB) for the characterization of cell interactions with 3D scaffolds obtained by different fabrication techniques is reported for the first time. The results clearly show the capability of the developed approach to preserve and finely resolve scaffold–cell interfaces highlighting details such as plasma membrane arrangement, extracellular matrix architecture and composition, and cellular structures playing a role in cell adhesion to the surface. It is anticipated that the developed approach will be relevant for the design of efficient cell‐instructive platforms in the study of cellular guidance strategies for tissue‐engineering applications as well as for in vitro 3D models.

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3D culture models of tissues under tension

Cited by 48 publications

References 110 publications

Bone marrow-derived stem/stromal cells (BMSC) 3D microtissues cultured in BMP-2 supplemented osteogenic induction medium are prone to adipogenesis

Bone marrow-derived stem/stromal cells (BMSC) 3D microtissues cultured in BMP-2 supplemented osteogenic induction medium are prone to adipogenesis

Lymphocyte mechanotransduction: The regulatory role of cytoskeletal dynamics in signaling cascades and effector functions

Electron Microscopy for 3D Scaffolds–Cell Biointerface Characterization

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