70 results on '"Frith, Jessica E."'
Search Results
52. Derivation of Mesenchymal Stromal Cells from Canine Induced Pluripotent Stem Cells by Inhibition of the TGFβ/Activin Signaling Pathway
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Whitworth, Deanne J., primary, Frith, Jessica E., additional, Frith, Thomas J.R., additional, Ovchinnikov, Dmitry A., additional, Cooper-White, Justin J., additional, and Wolvetang, Ernst J., additional
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- 2014
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53. Concise Review: New Frontiers in MicroRNA-Based Tissue Regeneration
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Frith, Jessica E., primary, Porrello, Enzo R., additional, and Cooper-White, Justin J., additional
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- 2014
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54. Microbioreactor Array Screening of Wnt Modulators and Microenvironmental Factors in Osteogenic Differentiation of Mesenchymal Progenitor Cells
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Frith, Jessica E., primary, Titmarsh, Drew M., additional, Padmanabhan, Harish, additional, and Cooper-White, Justin J., additional
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- 2013
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55. Lateral spacing of adhesion peptides influences human mesenchymal stem cell behaviour
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Frith, Jessica E., primary, Mills, Richard J., additional, and Cooper-White, Justin J., additional
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- 2012
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56. Effect of Geometric Challenges on Cell Migration
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Mills, Richard J., primary, Frith, Jessica E., additional, Hudson, James E., additional, and Cooper-White, Justin J., additional
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- 2011
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57. A Defined Medium and Substrate for Expansion of Human Mesenchymal Stromal Cell Progenitors That Enriches for Osteo- and Chondrogenic Precursors
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Hudson, James E., primary, Mills, Richard J., additional, Frith, Jessica E., additional, Brooke, Gary, additional, Jaramillo-Ferrada, Pamela, additional, Wolvetang, Ernst J., additional, and Cooper-White, Justin J., additional
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- 2011
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58. Dynamic Three-Dimensional Culture Methods Enhance Mesenchymal Stem Cell Properties and Increase Therapeutic Potential
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Frith, Jessica E., primary, Thomson, Brian, additional, and Genever, Paul G., additional
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- 2010
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59. Precision Surface Microtopography Regulates Cell Fate Via Changes To Actomyosin Contractility And Nuclear Architecture
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Carthew, James, Abdelmaksoud, Hazem H., Hodgson-Garms, Margeaux, Aslanoglou, Stella, Ghavamian, Sara, Elnathan, Roey, Spatz, Joachim P., Brugger, Jurgen, Thissen, Helmut, Voelcker, Nicolas H., and Frith, Jessica E.
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mesenchymal stem ,microtopography ,mechanotransduction ,stromal cells ,osteogenesis - Abstract
Cells are able to perceive complex mechanical cues from their microenvironment, which in turn influences their development. Although the understanding of these intricate mechanotransductive signals is evolving, the precise roles of substrate microtopography in directing cell fate is still poorly understood. Here, UV nanoimprint lithography is used to generate micropillar arrays ranging from 1 to 10 mu m in height, width, and spacing to investigate the impact of microtopography on mechanotransduction. Using mesenchymal stem cells (MSCs) as a model, stark pattern-specific changes in nuclear architecture, lamin A/C accumulation, chromatin positioning, and DNA methyltransferase expression, are demonstrated. MSC osteogenesis is also enhanced specifically on micropillars with 5 mu m width/spacing and 5 mu m height. Intriguingly, the highest degree of osteogenesis correlates with patterns that stimulated maximal nuclear deformation which is shown to be dependent on myosin-II-generated tension. The outcomes determine new insights into nuclear mechanotransduction by demonstrating that force transmission across the nuclear envelope can be modulated by substrate topography, and that this can alter chromatin organisation and impact upon cell fate. These findings have potential to inform the development of microstructured cell culture substrates that can direct cell mechanotransduction and fate for therapeutic applications in both research and clinical sectors.
60. Mechanical Properties and In Vitro Behavior of Additively Manufactured and Functionally Graded Ti6Al4V Porous Scaffolds.
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Onal, Ezgi, Frith, Jessica E., Jurg, Marten, Molotnikov, Andrey, and Wu, Xinhua
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BIOMATERIALS ,BODY centered cubic structure ,POROSITY ,TISSUE engineering ,COMPUTER-aided design - Abstract
Functionally graded lattice structures produced by additive manufacturing are promising for bone tissue engineering. Spatial variations in their porosity are reported to vary the stiffness and make it comparable to cortical or trabecular bone. However, the interplay between the mechanical properties and biological response of functionally graded lattices is less clear. Here we show that by designing continuous gradient structures and studying their mechanical and biological properties simultaneously, orthopedic implant design can be improved and guidelines can be established. Our continuous gradient structures were generated by gradually changing the strut diameter of a body centered cubic (BCC) unit cell. This approach enables a smooth transition between unit cell layers and minimizes the effect of stress discontinuity within the scaffold. Scaffolds were fabricated using selective laser melting (SLM) and underwent mechanical and in vitro biological testing. Our results indicate that optimal gradient structures should possess small pores in their core (~900 µm) to increase their mechanical strength whilst large pores (~1100 µm) should be utilized in their outer surface to enhance cell penetration and proliferation. We suggest this approach could be widely used in the design of orthopedic implants to maximize both the mechanical and biological properties of the implant. [ABSTRACT FROM AUTHOR]
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- 2018
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61. Fluorescent and Magnetic Mesoporous Hybrid Material: A Chemical and Biological Nanosensor for Hg2+ Ions.
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Suresh, Moorthy, Anand, Chokkalingam, Frith, Jessica E., Dhawale, Dattatray S., Subramaniam, Vishnu P., Strounina, Ekaterina, Sathish, Clastinrusselraj I., Yamaura, Kazunari, Cooper-White, Justin J., and Vinu, Ajayan
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- 2016
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62. Emerging biomaterials and technologies to control stem cell fate and patterning in engineered 3D tissues and organoids
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Mojtaba Farahani, James Carthew, Sanchyan Bhowmik, Chloe Shard, Ana Nunez-Nescolarde, Guillermo A. Gomez, Victor J. Cadarso, Alexander N. Combes, Jessica E. Frith, Farahani, Mojtaba, Carthew, James, Bhowmik, Sanchyan, Shard, Chloe, Nunez-Nescolarde, Ana, Gomez, Guillermo A, Cadarso, Victor J, Combes, Alexander N, and Frith, Jessica E
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Tissue Engineering ,growth ,Stem Cells ,Bioprinting ,General Physics and Astronomy ,Biocompatible Materials ,kidney organoids ,General Chemistry ,in-vitro ,self-organization ,General Biochemistry, Genetics and Molecular Biology ,culture ,Biomaterials ,Organoids ,mimicking ,scaffolds ,manipulation ,Printing, Three-Dimensional ,microfluidic-based generation ,Humans ,General Materials Science ,hydrogels - Abstract
Refereed/Peer-reviewed The ability to create complex three-dimensional cellular models that can effectively replicate the structure and function of human organs and tissues in vitro has the potential to revolutionize medicine. Such models could facilitate the interrogation of developmental and disease processes underpinning fundamental discovery science, vastly accelerate drug development and screening, or even be used to create tissues for implantation into the body. Realization of this potential, however, requires the recreation of complex biochemical, biophysical, and cellular patterns of 3D tissues and remains a key challenge in the field. Recent advances are being driven by improved knowledge of tissue morphogenesis and architecture and technological developments in bioengineering and materials science that can create the multidimensional and dynamic systems required to produce complex tissue microenvironments. In this article, we discuss challenges for in vitro models of tissues and organs and summarize the current state-of-the art in biomaterials and bioengineered systems that aim to address these challenges. This includes both top-down technologies, such as 3D photopatterning, magnetism, acoustic forces, and cell origami, as well as bottom-up patterning using 3D bioprinting, microfluidics, cell sheet technology, or composite scaffolds. We illustrate the varying ways that these can be applied to suit the needs of different tissues and applications by focussing on specific examples of patterning the bone-tendon interface, kidney organoids, and brain cancer models. Finally, we discuss the challenges and future prospects in applying materials science and bioengineering to develop high-quality 3D tissue structures for in vitro studies. Published under an exclusive license by AIP Publishing.
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- 2022
63. Five Piconewtons: The Difference between Osteogenic and Adipogenic Fate Choice in Human Mesenchymal Stem Cells
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Alpha S. Yap, Pingping Han, Jessica E. Frith, Justin J. Cooper-White, Geraldine M. O'Neill, Guillermo A. Gomez, Han, Pingping, Frith, Jessica E, Gomez, Guillermo A, Yap, Alpha S, O'Neill, Geraldine M, and Cooper-White, Justin J
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rac1 GTP-Binding Protein ,Polymers ,Cellular differentiation ,General Physics and Astronomy ,RAC1 ,Core Binding Factor Alpha 1 Subunit ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Focal adhesion ,Extracellular matrix ,Osteogenesis ,Humans ,General Materials Science ,Cell Lineage ,Mechanotransduction ,Cytoskeleton ,beta Catenin ,mechanotransduction ,Adaptor Proteins, Signal Transducing ,Focal Adhesions ,Adipogenesis ,biology ,Chemistry ,Mesenchymal stem cell ,General Engineering ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Mesenchymal Stem Cells ,YAP-Signaling Proteins ,Vinculin ,focal adhesions ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Cell biology ,Extracellular Matrix ,Cellular Microenvironment ,biology.protein ,mechanosensing ,lateral ligand spacing ,0210 nano-technology ,stem cell fate ,Signal Transduction ,Transcription Factors - Abstract
The ability of mesenchymal stem cells to sense nanoscale variations in extracellular matrix (ECM) compositions in their local microenvironment is crucial to their survival and their fate; however, the underlying molecular mechanisms defining how such fates are temporally modulated remain poorly understood. In this work, we have utilized self-assembled block copolymer surfaces to present nanodomains of an adhesive peptide found in many ECM proteins at different lateral spacings (from 30 to 60 nm) and studied the temporal response (2 h to 14 days) of human mesenchymal stem cells (hMSCs) using a panel of real-time localization and activity biosensors. Our findings revealed that within the first 4 to 24 h postadhesion and spreading, hMSCs on smaller nanodomain spacings recruit more activated FAK and Src proteins to produce larger, longer-lived, and increased numbers of focal adhesions (FAs). The adhesions formed on smaller nanospacings rapidly recruit higher amounts of nonmuscle myosin IIA and vinculin and experience tension forces (by >5 pN/FA) significantly higher than those observed on larger nanodomain spacings. The transmission of higher levels of tension into the cytoskeleton at short times was accompanied by higher Rac1, cytosolic β-catenin, and nuclear localization of YAP/TAZ and RUNX2, which together biased the commitment of hMSCs to an osteogenic fate. This investigation provides mechanistic insights to confirm that smaller lateral spacings of adhesive nanodomains alter hMSC mechanosensing and biases mechanotransduction at short times via differential coupling of FAK/Src/Rac1/myosin IIA/YAP/TAZ signaling pathways to support longer-term changes in stem cell differentiation and state Refereed/Peer-reviewed
- Published
- 2019
64. Mechanically-sensitive miRNAs bias human mesenchymal stem cell fate via mTOR signalling
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Jessica E. Frith, Fanyi Li, James Carthew, Nicole Cloonan, Guillermo A. Gomez, Gina D. Kusuma, Justin J. Cooper-White, Frith, Jessica E, Kusuma, Gina D, Carthew, James, Li, Fanyi, Cloonan, Nicole, Gomez, Guillermo A, and Cooper-White, Justin J
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0301 basic medicine ,RHOA ,novel strategy ,Cellular differentiation ,Science ,General Physics and Astronomy ,macromolecular substances ,complex mixtures ,Mechanotransduction, Cellular ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Osteogenesis ,Humans ,Mechanotransduction ,lcsh:Science ,PI3K/AKT/mTOR pathway ,Cells, Cultured ,Cell Proliferation ,Multidisciplinary ,Microscopy, Confocal ,biology ,Tissue Engineering ,Chemistry ,mesenchymal stem cell (MSC) ,TOR Serine-Threonine Kinases ,Mesenchymal stem cell ,fungi ,technology, industry, and agriculture ,food and beverages ,matrix mechanics ,Cell Differentiation ,Hydrogels ,Mesenchymal Stem Cells ,General Chemistry ,Cell biology ,MicroRNAs ,030104 developmental biology ,Gene Expression Regulation ,Self-healing hydrogels ,biology.protein ,Mechanosensitive channels ,lcsh:Q ,Signal transduction ,Signal Transduction - Abstract
Mechanotransduction is a strong driver of mesenchymal stem cell (MSC) fate. In vitro, variations in matrix mechanics invoke changes in MSC proliferation, migration and differentiation. However, when incorporating MSCs within injectable, inherently soft hydrogels, this dominance over MSC response substantially limits our ability to couple the ease of application of hydrogels with efficiently directed MSC differentiation, especially in the case of bone generation. Here, we identify differential miRNA expression in response to varying hydrogel stiffness and RhoA activity. We show that modulation of miR-100-5p and miR-143-3p can be used to bias MSC fate and provide mechanistic insight by demonstrating convergence on mTOR signalling. By modulating these mechanosensitive miRNAs, we can enhance osteogenesis in a soft 3D hydrogel. The outcomes of this study provide new understanding of the mechanisms regulating MSC mechanotransduction and differentiation, but also a novel strategy with which to drive MSC fate and significantly impact MSC-based tissue-engineering applications., Mesenchymal stem cell (MSC) fate can be mechanically regulated by substrate stiffness but this is difficult to control in a 3D hydrogel. Here the authors identify miRNAs that change expression in response to substrate stiffness and RhoA signalling and show that they can bias MSC fate in a 3D soft hydrogel.
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- 2018
65. Fluorescent and Magnetic Mesoporous Hybrid Material: A Chemical and Biological Nanosensor for Hg2+ Ions
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Ajayan Vinu, Jessica E. Frith, Vishnu Priya Subramaniam, Ekaterina Strounina, Clastinrusselraj Indirathankam Sathish, Dattatray S. Dhawale, Justin J. Cooper-White, Moorthy Suresh, Kazunari Yamaura, Chokkalingam Anand, Moorthy, Suresh, Chokkalingam, Anand, Frith, Jessica E, Dhawale, Dattatray S, Subramaniam, Vishnu P, Strounina, Ekaterina, Sathish, Clastinrusselraj I, Yamaura, Kazunari, Cooper-White, Justin J, and Vinu, Ajayan
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Materials science ,Fluorophore ,Nanoparticle ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,Rhodamine ,chemistry.chemical_compound ,Mice ,Nanocages ,X-Ray Diffraction ,Nanosensor ,Animals ,Magnetite Nanoparticles ,Fluorescent Dyes ,Ions ,Multidisciplinary ,mesoporous material ,Nanoporous ,Rhodamines ,Mercury ,Silanes ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Nanostructures ,Spectrometry, Fluorescence ,chemistry ,Microscopy, Fluorescence ,Metals ,NIH 3T3 Cells ,0210 nano-technology ,Hybrid material ,Mesoporous material ,Porosity - Abstract
We introduce “sense, track and separate” approach for the removal of Hg2+ ion from aqueous media using highly ordered and magnetic mesoporous ferrosilicate nanocages functionalised with rhodamine fluorophore derivative. These functionalised materials offer both fluorescent and magnetic properties in a single system which help not only to selectively sense the Hg2+ ions with a high precision but also adsorb and separate a significant amount of Hg2+ ion in aqueous media. We demonstrate that the magnetic affinity of these materials, generated from the ultrafine γ-Fe2O3 nanoparticles present inside the nanochannels of the support, can efficiently be used as a fluorescent tag to sense the Hg2+ ions present in NIH3T3 fibroblasts live cells and to track the movement of the cells by external magnetic field monitored using confocal fluorescence microscopy. This simple approach of introducing multiple functions in the magnetic mesoporous materials raise the prospect of creating new advanced functional materials by fusing organic, inorganic and biomolecules to create advanced hybrid nanoporous materials which have a potential use not only for sensing and the separation of toxic metal ions but also for cell tracking in bio-separation and the drug delivery.
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- 2016
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66. Effects of bound versus soluble pentosan polysulphate in PEG/HA-based hydrogels tailored for intervertebral disc regeneration
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Jessica E. Frith, Darryl L. Whitehead, Justin J. Cooper-White, Donna J. Menzies, Peter Ghosh, Andrew Ross Cameron, Stan Gronthos, Andrew C.W. Zannettino, Frith, Jessica E, Menzies, Donna J, Cameron, Andrew R, Ghosh, P, Whitehead, Darryl L, Gronthos, S, Zannettino, Andrew CW, and Cooper-White, Justin J
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Materials science ,Cell Survival ,education ,Biophysics ,Bioengineering ,Biocompatible Materials ,Matrix (biology) ,Cell Line ,Polyethylene Glycols ,Biomaterials ,chemistry.chemical_compound ,Tissue engineering ,Hyaluronic acid ,PEG ratio ,hyaluronic acid ,medicine ,Humans ,Regeneration ,Hyaluronic Acid ,Intervertebral Disc ,health care economics and organizations ,Cell Proliferation ,Pentosan Sulfuric Polyester ,Tissue Engineering ,nucleus pulposus ,Cell Differentiation ,Hydrogels ,Mesenchymal Stem Cells ,pentosan polysulphate ,chemistry ,Solubility ,Mechanics of Materials ,Cell culture ,Self-healing hydrogels ,Ceramics and Composites ,Swelling ,medicine.symptom ,hydrogel ,Ethylene glycol ,Biomedical engineering ,mesenchymal progenitor cell - Abstract
Previous reports in the literature investigating chondrogenesis in mesenchymal progenitor cell (MPC) cultures have confirmed the chondro-inductive potential of pentosan polysulphate (PPS), a highly sulphated semi-synthetic polysaccharide, when added as a soluble component to culture media under standard aggregate-assay conditions or to poly(ethylene glycol)/hyaluronic acid (PEG/HA)-based hydrogels, even in the absence of inductive factors (e.g. TGFβ). In this present study, we aimed to assess whether a 'bound' PPS would have greater activity and availability over a soluble PPS, as a media additive or when incorporated into PEG/HA-based hydrogels. We achieved this by covalently pre-binding the PPS to the HA component of the gel (forming a new molecule, HA-PPS). We firstly investigated the activity of HA-PPS compared to free PPS, when added as a soluble factor to culture media. Cell proliferation, as determined by CCK8 and EdU assay, was decreased in the presence of either bound or free PPS whilst chondrogenic differentiation, as determined by DMMB assay and histology, was enhanced. In all cases, the effect of the bound PPS (HA-PPS) was more potent than that of the unbound form. These results alone suggest wider applications for this new molecule, either as a culture supplement or as a coating for scaffolds targeted at chondrogenic differentiation or maturation. We then investigated the incorporation of HA-PPS into a PEG/HA-based hydrogel system, by simply substituting some of the HA for HA-PPS. Rheological testing confirmed that incorporation of either HA-PPS or PPS did not significantly affect gelation kinetics, final hydrogel modulus or degradation rate but had a small, but significant, effect on swelling. When encapsulated in the hydrogels, MPCs retained good viability and rapidly adopted a rounded morphology. Histological analysis of both GAG and collagen deposition after 21 days showed that the incorporation of the bound-PPS into the hydrogel resulted in increased matrix formation when compared to the addition of soluble PPS to the hydrogel, or the hydrogel alone. We believe that this new generation injectable, degradable hydrogel, incorporating now a covalently bound-PPS, when combined with MPCs, has the potential to assist cartilage regeneration in a multitude of therapeutic targets, including for intervertebral disc (IVD) degeneration. Refereed/Peer-reviewed
- Published
- 2014
67. The effect of time-dependent deformation of viscoelastic hydrogels on myogenic induction and Rac1 activity in mesenchymal stem cells
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Guillermo A. Gomez, Andrew Ross Cameron, Justin J. Cooper-White, Jessica E. Frith, Alpha S. Yap, Cameron, Andrew R, Frith, Jessica E, Gomez, Guillermo A, Yap, Alpha S, and Cooper-White, Justin J
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Materials science ,RHOA ,Cellular differentiation ,Myocytes, Smooth Muscle ,Materials Science ,Biophysics ,Bioengineering ,Mechanotransduction, Cellular ,Viscoelasticity ,creep ,Biomaterials ,Engineering ,Humans ,Mechanotransduction ,Engineering, Biomedical ,Cells, Cultured ,mesenchymal stem cell ,smooth muscle cell ,viscoelasticity ,mechanotransduction ,Materials Science, Biomaterials ,biology ,Mesenchymal stem cell ,Cell Differentiation ,Hydrogels ,Mesenchymal Stem Cells ,Adhesion ,Mechanics of Materials ,Self-healing hydrogels ,Ceramics and Composites ,biology.protein ,Stem cell ,hydrogel ,Biomedical engineering - Abstract
Cell behaviours within tissues are influenced by a broad array of physical and biochemical microenvironmental factors. Whilst 'stiffness' is a recognised physical property of substrates and tissue microenvironments that influences many cellular behaviours, tissues and their extracellular matrices are not purely rigid but 'viscoelastic' materials, composed of both rigid-like (elastic) and dissipative (viscous) elements. This viscoelasticity results in materials displaying increased deformation with time under the imposition of a defined force or stress, a phenomenon referred to as time-dependent deformation or 'creep'. Previously, we compared the behaviour of human mesenchymal stem cells (hMSCs) on hydrogels tailored to have a constant stiffness, but to display varying levels of creep in response to an applied force. Using polyacrylamide as a model material, we showed that on high-creep hydrogels (HCHs), hMSCs displayed increased proliferation, spread area and differentiation towards multiple lineages, compared to their purely stiff analogue, with a particular propensity for differentiation towards a smooth muscle cell (SMC) lineage. In this present study, we investigate the mechanisms behind this phenomenon and show that hMSCs adhered to HCHs have increased expression of SMC induction factors, including soluble factors, ECM proteins and the cell cell adhesion molecule, N-Cadherin. Further, we identify a key role for Rac1 signalling in mediating this increased N-Cadherin expression. Using a real-time Rac1-FRET biosensor, we confirm increased Rac1 activation on HCHs, an observation that is further supported functionally by observed increases in motility and lamellipodial protrusion rates of hMSCs. Increased Rac1 activity in hMSCs on HCHs provides underlying mechanisms for enhanced commitment towards a SMC lineage and the compensatory increase in spread area (isotonic tension) after a creep-induced loss of cytoskeletal tension on viscoelastic substrates, in contrast to previous studies that have consistently demonstrated up-regulation of RhoA activity with increasing substrate stiffness. Tuning substrate viscoelasticity to introduce varying levels of creep thus equips the biomaterial scientist or engineer with a new tool with which to tune and direct stem cell outcomes. Refereed/Peer-reviewed
- Published
- 2014
68. An injectable hydrogel incorporating mesenchymal precursor cells and pentosan polysulphate for intervertebral disc regeneration
- Author
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Darryl L. Whitehead, Jessica E. Frith, Justin J. Cooper-White, Andrew C.W. Zannettino, Peter Ghosh, Donna J. Menzies, Stan Gronthos, Andrew Ross Cameron, Frith, Jessica E, Cameron, Andrew R, Menzies, Donna J, Ghosh, Peter, Whitehead, Darryl L, Gronthos, Stan, Zannettino, Andrew, and Cooper-White, Justin J
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Materials science ,Biophysics ,Bioengineering ,Biocompatible Materials ,Matrix (biology) ,Mesenchymal Stem Cell Transplantation ,Hydrogel, Polyethylene Glycol Dimethacrylate ,Cell Line ,Injections ,Biomaterials ,chemistry.chemical_compound ,Tissue engineering ,Hyaluronic acid ,medicine ,Animals ,Humans ,Regeneration ,Rats, Wistar ,Intervertebral Disc ,Pentosan Sulfuric Polyester ,Regeneration (biology) ,nucleus pulposus ,Intervertebral disc ,Mesenchymal Stem Cells ,Chondrogenesis ,Rats ,pentosan polysulphate ,medicine.anatomical_structure ,chemistry ,fibrocartilage ,Mechanics of Materials ,Self-healing hydrogels ,Ceramics and Composites ,Fibrocartilage ,Female ,hydrogel ,Biomedical engineering ,mesenchymal progenitor cell - Abstract
Intervertebral disc (IVD) degeneration is one of the leading causes of lower back pain and a major health problem worldwide. Current surgical treatments include excision or immobilisation, with neither approach resulting in the repair of the degenerative disc. As such, a tissue engineering-based approach in which stem cells, coupled with an advanced delivery system, could overcome this deficiency and lead to a therapy that encourages functional fibrocartilage generation in the IVD. In this study, we have developed an injectable hydrogel system based on enzymatically-crosslinked polyethylene glycol and hyaluronic acid. We examined the effects of adding pentosan polysulphate (PPS), a synthetic glycosaminoglycan-like factor that has previously been shown (in vitro and in vivo) to this gel system in order to induce chondrogenesis in mesenchymal precursor cells (MPCs) when added as a soluble factor, even in the absence of additional growth factors such as TGF-β. We show that both the gelation rate and mechanical strength of the resulting hydrogels can be tuned in order to optimise the conditions required to produce gels with the desired combination of properties for an IVD scaffold. Human immunoselected STRO-1+ MPCs were then incorporated into the hydrogels. They were shown to retain good viability after both the initial formation of the gel and for longer-term culture periods in vitro. Furthermore, MPC/hydrogel composites formed cartilage-like tissue which was significantly enhanced by the incorporation of PPS into the hydrogels, particularly with respect to the deposition of type-II-collagen. Finally, using a wild-type rat subcutaneous implantation model, we examined the extent of any immune reaction and confirmed that this matrix is well tolerated by the host. Together these data provide evidence that such a system has significant potential as both a delivery vehicle for MPCs and as a matrix for fibrocartilage tissue engineering applications. Refereed/Peer-reviewed
- Published
- 2013
69. Creation of Grooved Tissue Engineering Scaffolds from Architectured Multilayer Polymer Composites by a Tuneable One-Step Degradation Process.
- Author
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Vellayappan MV, Duarte F, Sollogoub C, Dirrenberger J, Guinault A, Frith JE, Parkington HC, Molotnikov A, and Cameron NR
- Abstract
The surface properties of biomaterials interact directly with biological systems, influencing cellular responses, tissue integration, and biocompatibility. Surface topography plays a critical role in cardiac tissue engineering by affecting electrical conductivity, cardiomyocyte alignment, and contractile function. Current methods for controlling surface properties and topography in cardiac tissue engineering scaffolds are limited, expensive, and lack precision. This study introduces a low-cost, one-step degradation process to create scaffolds with well-defined micro-grooves from multilayered 3D printed poly(lactic acid)/thermoplastic polyurethane composites. The approach provides control over erosion rate and surface morphology, allowing easy tuning of scaffold topographical cues for tissue engineering applications. The findings reported in this study provide a library of easily tuneable scaffold topographical cues. A strong dependence of neonatal rat cardiomyocyte (NRCM) contact guidance with the multilayers' dimension and shape in partially degraded polylactic acid (PLA)/thermoplastic polyurethane (TPU) samples is observed. NRCMs cultured on samples with a layer thickness of 13 ± 2 µm and depth of 4.7 ± 0.2 µm demonstrate the most regular contractions. Hence, the proposed fabrication scheme can be used to produce a new generation of biomaterials with excellent controllability determined by multilayer thickness, printing parameters, and degradation treatment duration., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)
- Published
- 2024
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70. Three-dimensional in vitro culture techniques for mesenchymal stem cells.
- Author
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Saleh FA, Frith JE, Lee JA, and Genever PG
- Subjects
- Cell Survival, Coculture Techniques, Cryopreservation, Flow Cytometry, Genetic Vectors genetics, Humans, Lentivirus genetics, Liver cytology, Mesenchymal Stem Cells metabolism, Spheroids, Cellular cytology, Staining and Labeling, Telomerase genetics, Telomerase metabolism, Cell Culture Techniques methods, Mesenchymal Stem Cells cytology
- Abstract
In recent years there has been a growing interest in culturing adherent cells using three-dimensional (3D) techniques, rather than more conventional 2D culture methods. This interest emerges from the realization that growing cells on plastic surfaces cannot truly re-create 3D in vivo conditions and therefore might be limiting the cells' potential. In addition, adult stem cells exist in specialized microenvironments, or niches, where the spatial organization of different niche elements (such as different cell types, extracellular matrix) contributes significantly to stem cell maintenance, which cannot be represented using 2D in vitro models. We have generated a range of different 3D approaches for the analysis of mesenchymal stem cells (MSCs) using both mono- and co-culture environments.
- Published
- 2012
- Full Text
- View/download PDF
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