Wharton's Jelly human Mesenchymal Stem Cell contact guidance by noisy nanotopographies

Jacchetti, Emanuela; Rienzo, Carmine Di; Meucci, Sandro; Nocchi, Francesca Romana; Beltram, Fabio; Cecchini, Marco

doi:10.1038/srep03830

Cited by 18 publications

(18 citation statements)

References 62 publications

(72 reference statements)

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“…All the COC surfaces were proven to be adhesive for MPCs without requiring any chemical functionalization but plasma activation. In this study and previously (Tonazzini et al, 2013; Jacchetti et al, 2014) we did not find any cytotoxicity originating by either the surface topographical modification or by the material itself. Finally, standard tissue culture Petri dishes were also used as control condition for the FLAT substrates in order to verify that the material itself did not cause the MPC-MSC transition.…”

Section: Resultssupporting

confidence: 75%

Nanotopography Induced Human Bone Marrow Mesangiogenic Progenitor Cells (MPCs) to Mesenchymal Stromal Cells (MSCs) Transition

Abednatanzi

Montali

Jacchetti

et al. 2016

Front. Cell Dev. Biol.

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Mesangiogenic progenitor cells (MPCs) are a very peculiar population of cells present in the human adult bone marrow, only recently discovered and characterized. Owing to their differentiation potential, MPCs can be considered progenitors for mesenchymal stromal cells (MSCs), and for this reason they potentially represent a promising cell population to apply for skeletal tissue regeneration applications. Here, we evaluate the effects of surface nanotopography on MPCs, considering the possibility that this specific physical stimulus alone can trigger MPC differentiation toward the mesenchymal lineage. In particular, we exploit nanogratings to deliver a mechanical, directional stimulus by contact interaction to promote cell morphological polarization and stretching. Following this interaction, we study the MPC-MSC transition by i. analyzing the change in cell morphotype by immunostaining of the key cell-adhesion structures and confocal fluorescence microscopy, and ii. quantifying the expression of cell-phenotype characterizing markers by flow cytometry. We demonstrate that the MPC mesengenic differentiation can be induced by the solely interaction with the NGs, in absence of any other external, chemical stimulus. This aspect is of particular interest in the case of multipotent progenitors as MPCs that, retaining both mesengenic and angiogenic potential, possess a high clinical appeal.

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Section: Resultssupporting

confidence: 75%

Nanotopography Induced Human Bone Marrow Mesangiogenic Progenitor Cells (MPCs) to Mesenchymal Stromal Cells (MSCs) Transition

Abednatanzi

Montali

Jacchetti

et al. 2016

Front. Cell Dev. Biol.

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“…Results from 2D cell cultures on planar substrates have previously led to values of 700 μm/day, while the use of micro-patterned grooves has promoted a velocity of up to 1000 μm/day and encouraged interest in using surface patterns to promote cell culture strategies [47]. Recent research has also demonstrated the beneficial use of anisotropic nanopatterns to drive stem cell migration and has shown cell velocity values of up to 960 μm/day along the direction parallel to the pattern and up to 600 μm/day along the direction perpendicular to the pattern [48]. The results are in accordance with the behavior of hMSCs.…”

mentioning

confidence: 99%

“…In the microsystem, hMSCs reach a velocity value of 6000 µm/day, helping to show the positive impact of incorporating design-defined fractal microtextures to promote cell motility and eventual tissue growth. Results from 2D cell cultures on planar substrates have previously led to values of 700 µm/day, while the use of micro-patterned grooves has promoted a velocity of up to Recent research has also demonstrated the beneficial use of anisotropic nanopatterns to drive stem cell migration and has shown cell velocity values of up to 960 µm/day along the direction parallel to the pattern and up to 600 µm/day along the direction perpendicular to the pattern [48].…”

mentioning

confidence: 99%

“…According to Doyle and colleagues, cell migration in both 1D and 3D is rapid, uniaxial, and independent of extra-cellular matrix ligand density, in contrast to 2D cultures, which brings out the need for alternative solutions aimed at a more adequate reproduction of the 3D environment [48]. We truly believe that our approach of providing 1D cell culture along channels with inner three-dimensional features can help with further studies linked to comparing 1D, 2D, and 3D cell culture, as well as take into account non-integer values, using a fractal-based definition of dimension.…”

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confidence: 99%

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Multi-Channeled Polymeric Microsystem for Studying the Impact of Surface Topography on Cell Adhesion and Motility

2015

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This paper presents the complete development and experimental validation of a microsystem designed to systematically assess the impact of surface topography on cell adhesion and dynamics. The microsystem includes two pools for culturing cells and for including chemicals. These pools are connected by several channels that have different microtextures, along which the cells crawl from one well to another. The impact of channel surface topography on cell performance, as well as the influence of other relevant factors, can therefore be assessed. The microsystem stands out for its being able to precisely define the surface topographies from the design stage and also has the advantage of including the different textures under study in a single device. Validation has been carried out by culturing human mesenchymal stem cells (hMSCs) on the microsystem pre-treated with a coating of hMSC conditioned medium (CM) produced by these cells. The impact of surface topography on cell adhesion, motility, and velocity has been quantified, and the relevance of using a coating of hMSC-CM for these kinds of studies has been analyzed. Main results, current challenges, and future proposals based on the use of the proposed microsystem as an experimental resource for studying cell mechanobiology are also presented.

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“…9,40 The degree to which cells engage in contact guidance is intimately related to the degree of collagen fiber alignment and consequently the noise in the contact guidance signal. 17,51 However, collagen fiber alignment dynamically changes over time due to both contractility and MMP activity of stromal cells in the tumor microenvironment. Cancer cells can also remodel collagen fibers during the process of migration.…”

Section: Discussionmentioning

confidence: 99%

Degradation and Remodeling of Epitaxially Grown Collagen Fibrils

et al. 2018

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Introduction— The extracellular matrix (ECM) in the tumor microenvironment contains high densities of collagen that are highly aligned, resulting in directional migration called contact guidance that facilitates efficient migration out of the tumor. Cancer cells can remodel the ECM through traction force controlled by myosin contractility or proteolytic activity controlled by matrix metalloproteinase (MMP) activity, leading to either enhanced or diminished contact guidance. Methods— Recently, we have leveraged the ability of mica to epitaxially grow aligned collagen fibrils in order to assess contact guidance. In this article, we probe the mechanisms of remodeling of aligned collagen fibrils on mica by breast cancer cells. Results— We show that cells that contact guide with high fidelity (MDA-MB-231 cells) exert more force on the underlying collagen fibrils than do cells that contact guide with low fidelity (MTLn3 cells). These high traction cells (MDA-MB-231 cells) remodel collagen fibrils over hours, pulling so hard that the collagen fibrils detach from the surface, effectively delaminating the entire contact guidance cue. Myosin or MMP inhibition decreases this effect. Interestingly, blocking MMP appears to increase the alignment of cells on these substrates, potentially allowing the alignment through myosin contractility to be uninhibited. Finally, amplification or dampening of contact guidance with respect to a particular collagen fibril organization is seen under different conditions. Conclusions— Both myosin II contractility and MMP activity allow MDA-MB-231 cells to remodel and eventually destroy epitaxially grown aligned collagen fibrils.

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Wharton's Jelly human Mesenchymal Stem Cell contact guidance by noisy nanotopographies

Cited by 18 publications

References 62 publications

Nanotopography Induced Human Bone Marrow Mesangiogenic Progenitor Cells (MPCs) to Mesenchymal Stromal Cells (MSCs) Transition

Nanotopography Induced Human Bone Marrow Mesangiogenic Progenitor Cells (MPCs) to Mesenchymal Stromal Cells (MSCs) Transition

Multi-Channeled Polymeric Microsystem for Studying the Impact of Surface Topography on Cell Adhesion and Motility

Degradation and Remodeling of Epitaxially Grown Collagen Fibrils

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