A cell migration device that maintains a defined surface with no cellular damage during wound edge generation

Doran, Michael; Mills, Richard J.; Parker, Anthony James; Landman, Kerry A.; Cooper-White, Justin J.

doi:10.1039/b900791a

Cited by 44 publications

(42 citation statements)

References 21 publications

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“…To establish whether this was true, we used a microchannel migration device (Doran et al, 2009) to determine the migration rate of hMSCs on surfaces with different RGD spacings. The migration rate of the hMSCs was seen to increase as the spacing of the RGD increased from 34 to 50 nm, leading to a significantly higher migration speed on 50-nm-spaced peptides than on 34-nm-spaced peptides.…”

Section: Resultsmentioning

confidence: 99%

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Lateral spacing of adhesion peptides influences human mesenchymal stem cell behaviour

Frith

Mills

Cooper-White

2012

Journal of Cell Science

142

157

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SummaryMesenchymal stem cells (MSCs) have attracted great interest in recent years for tissue engineering and regenerative medicine applications due to their ease of isolation and multipotent differentiation capacity. In the past, MSC research has focussed on the effects of soluble cues, such as growth factors and cytokines; however, there is now increasing interest in understanding how parameters such as substrate modulus, specific extracellular matrix (ECM) components and the ways in which these are presented to the cell can influence MSC properties. Here we use surfaces of self-assembled maleimide-functionalized polystyrene-blockpoly(ethylene oxide) copolymers (PS-PEO-Ma) to investigate how the spatial arrangement of cell adhesion ligands affects MSC behaviour. By changing the ratio of PS-PEO-Ma in mixtures of block copolymer and polystyrene homopolymer, we can create surfaces with lateral spacing of the PEO-Ma domains ranging from 34 to 62 nm. Through subsequent binding of cysteine-GRGDS peptides to the maleimide-terminated end of the PEO chains in each of these domains, we are able to present tailored surfaces of controlled lateral spacing of RGD (arginine-glycine-aspartic acid) peptides to MSCs. We demonstrate that adhesion of MSCs to the RGD-functionalized block-copolymer surfaces is through specific attachment to the presented RGD motif and that this is mediated by a5, aV, b1 and b3 integrins. We show that as the lateral spacing of the peptides is increased, the ability of the MSCs to spread is diminished and that the morphology changes from well-spread cells with normal fibroblastic morphology and defined stress-fibres, to less-spread cells with numerous cell protrusions and few stress fibres. In addition, the ability of MSCs to form mature focal adhesions is reduced on substrates with increased lateral spacing. Finally, we investigate differentiation and use qRT-PCR determination of gene expression levels and a quantitative alkaline phosphatase assay to show that MSC osteogenesis is reduced on surfaces with increased lateral spacing while adipogenic differentiation is increased. We show here, for the first time, that the lateral spacing of adhesion peptides affects human MSC (hMSC) properties and might therefore be a useful parameter with which to modify hMSC behaviour in future tissue engineering strategies.

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Section: Resultsmentioning

confidence: 99%

“…Cell migration was analysed using a multichannel migration device as previously described (Doran et al, 2009), see supplementary material Fig. S4.…”

Section: Cell Migrationmentioning

confidence: 99%

Lateral spacing of adhesion peptides influences human mesenchymal stem cell behaviour

Frith

Mills

Cooper-White

2012

Journal of Cell Science

142

157

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“…Figure 1A shows the silica wafer (100 mm diameter) used to cast the bodies of three microchannel migration devices simultaneously. The features on the silicon wafer (3 groups of 14 rectangular features, each 1 mm long, 500 µm wide, and 100 µm in height) were formed using SU-8 photo resist (SU8-2025, MicroChem, Newton, MA, USA) as per the manufacturer's instructions (and as described previously) [25]. A 4 mm deep layer of polydimethylsiloxane (PDMS, Sylgard, Dow Corning, Midland, TX, USA) was poured over the wafer surface and cured at 80 °C for 30 min.…”

Section: Cell Isolation and Culturementioning

confidence: 99%

In Vitro Assessment of Migratory Behavior of Two Cell Populations in a Simple Multichannel Microdevice

et al. 2013

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Recent literature suggests that mesenchymal stem/stromal cells (MSC) could be used as Trojan Horses to deliver "death-signals" to cancer cells. Herein, we describe the development of a novel multichannel cell migration device, and use it to investigate the relative migration rates of bone marrow-derived MSC and breast cancer cells (MCF-7) towards each other. Confluent monolayers of MSC and MCF-7 were established in adjacent chambers separated by an array of 14 microchannels. Initially, culture chambers were isolated by air bubbles (air-valves) contained within each microchannel, and then bubbles were displaced to initiate the assay. The MCF-7 cells migrated preferentially towards MSC, whilst the MSC did not migrate preferentially towards the MCF-7 cells. Our results corroborate previous literature that suggests MSC migration towards cancer cells in vivo is in response to the associated inflammation rather than directly to signals secreted by the cancer cells themselves. OPEN ACCESSProcesses 2013, 1 350

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“…The area is continuously photographed from the formation to the closure of the ''wound''. Nevertheless, the accuracy of experimental results is influenced to some extent by mechanical damage to cells and by cell debris produced during scraping (Doran et al 2009). Therefore, new ways of studying cell migration and their applications in specific cell migration assays are one of focuses of current research.…”

Section: Introductionmentioning

confidence: 99%

Microvalve and liquid membrane double-controlled integrated microfluidics for observing the interaction of breast cancer cells

Liu

Wang

et al. 2012

Microfluid Nanofluid

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The methodical development of cell biology has resulted in significant advancements in the study of breast tumors. However, the dynamic investigation of the self-seeding process remains largely out of reach. In the present study, we describe a microvalve and liquid membrane double-controlled integrated microfluidic device that provides for the versatile assessment of breast tumor cell invasion dynamics. The liquid membrane formation was first optimized to obtain a high level of control, and was then applied to different types of homotypic and heterotypic cell seeding with precise selective positioning for monoculture and coculture. Using this device, the interaction between breast cancer cells MDA231-LM2 and MDA-MB231 was successfully observed to investigate self-seeding dynamics, including migration, infiltration, and coexistence. The results quantitatively demonstrate the mutual signal-induced attraction between MDA-MB231 and MDA231-LM2 cells, as well as the progressive infiltration of MDA231-LM2 cells into the MDA-MB231 cell population. These results are valuable in the development of spatiotemporal-controlled microfluidic systems and to many microscale-based biological and diagnostic studies involving cell growth, cell differentiation, cell interaction, and cell signal.

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A cell migration device that maintains a defined surface with no cellular damage during wound edge generation

Cited by 44 publications

References 21 publications

Lateral spacing of adhesion peptides influences human mesenchymal stem cell behaviour

Lateral spacing of adhesion peptides influences human mesenchymal stem cell behaviour

In Vitro Assessment of Migratory Behavior of Two Cell Populations in a Simple Multichannel Microdevice

Microvalve and liquid membrane double-controlled integrated microfluidics for observing the interaction of breast cancer cells

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