Responses of keratinocytes to substrate-bound vitronectin:growth factor complexes

Hollier, Brett G.; Harkin, Damien G.; Leavesley, David I.; Upton, Zee

doi:10.1016/j.yexcr.2005.01.004

Cited by 34 publications

(27 citation statements)

References 50 publications

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“…There is also potential to combine established wound healing therapies with the nanoporous membrane to provide a superior topographical and physicochemical approach to wound healing. For example, substrate-bound vitronectin (VN): growth factor complexes have been shown to stimulate keratinocyte proliferation and migration 54,55 and increase reepithelialization of DDPT burn injuries in vivo. 20 Taken together, keratinocyte function may be further stimulated to drive repair by a membrane functionalized with the complexes.…”

Section: Further Applicationmentioning

confidence: 99%

The Effect of Nano-Scale Topography on Keratinocyte Phenotype and Wound Healing Following Burn Injury

Parkinson

Rea

Stevenson

et al. 2012

Tissue Engineering Part A

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Section: Further Applicationmentioning

confidence: 99%

The Effect of Nano-Scale Topography on Keratinocyte Phenotype and Wound Healing Following Burn Injury

Parkinson

Rea

Stevenson

et al. 2012

Tissue Engineering Part A

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“…For example, TSP-1 induces focal adhesion dissociation through calreticulin and phosphatidylinositol 3-kinase signaling (Goicoechea et al, 2000;Orr et al, 2002). Blockade of integrin interactions with ECM ligands has been reported previously (Hadari et al, 2000;Hughes, 2001;Wu et al, 2007) as well as indirect effects on adhesion through modulation of growth factor signaling (Bornstein and Sage, 2002;Hollier et al, 2005Hollier et al, , 2008. Finally, the FN-binding properties of tenascin-C reduce cell adhesion and modify intracellular signaling by preventing syndecan-4 receptor binding to the C-terminal heparin-binding (HepII) domain of FN (Huang et al, 2001;Orend et al, 2003;Midwood et al, 2004a).…”

Section: Introductionmentioning

confidence: 67%

A Shared Mechanism of Adhesion Modulation for Tenascin-C and Fibulin-1

Williams

Schwarzbauer

2009

MBoC

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Adhesion modulatory proteins are important effectors of cell-matrix interactions during tissue remodeling and regeneration. They comprise a diverse group of matricellular proteins that confer antiadhesive properties to the extracellular matrix (ECM). We compared the inhibitory effects of two adhesion modulatory proteins, fibulin-1 and tenascin-C, both of which bind to the C-terminal heparin-binding (HepII) domain of fibronectin (FN) but are structurally distinct. Here, we report that, like tenascin-C, fibulin-1 inhibits fibroblast spreading and cell-mediated contraction of a fibrin-FN matrix. These proteins act by modulation of focal adhesion kinase and extracellular signal-regulated kinase signaling. The inhibitory effects were bypassed by lysophosphatidic acid, an activator of RhoA GTPase. Fibroblast response to fibulin-1, similar to tenascin-C, was dependent on expression of the heparan sulfate proteoglycan syndecan-4, which also binds to the HepII domain. Therefore, blockade of HepII-mediated signaling by competitive binding of fibulin-1 or tenascin-C represents a shared mechanism of adhesion modulation among disparate modulatory proteins. INTRODUCTIONTissue architecture is determined by positioning of cells within the fibrillar assemblage of proteins, proteoglycans, and other components that comprise the extracellular matrix (ECM). Organization and composition of the ECM have significant impacts on many cellular functions. By binding to transmembrane receptors, individual ECM components affect cell arrangements and initiate signaling events that alter gene expression and regulate cell communication. Fibronectin (FN) is a ubiquitously expressed, multifunctional ECM glycoprotein that promotes cell adhesion and plays important roles in tissue development, repair, and remodeling (Hynes, 1990). Cell interactions with FN are largely dependent on integrin receptors with subsequent engagement of intracellular signaling and cytoskeletal components (Hynes, 2002). Tissue development and remodeling require changes in cell adhesion to allow cell proliferation, cell motility, and ECM reorganization (Singer and Clark, 1999). Modulation of cell adhesion can be achieved by modifications in FN matrix organization or composition (Sechler et al., 1998;Midwood et al., 2006) or by the deposition of adhesion modulatory or matricellular proteins (Bornstein and Sage, 2002), including tenascin-C, fibulin-1, thrombospondin-1 (TSP-1), and many others (Fassler et al., 1996;Bornstein, 2001;Chiquet-Ehrismann and Chiquet, 2003;Midwood et al., 2004b).Expression of proteins that modulate cell adhesion causes reduced cell interactions with adhesive ECM, thus allowing cell movement, shape changes, proliferation, and other related processes (Chiquet-Ehrismann, 1991;Orend and Chiquet-Ehrismann, 2000). The suppression of adhesion-related signal transduction produces dramatic changes in cytoskeletal organization and in the kinetics of cell contact with the ECM. Adhesion modulatory proteins comprise an increasingly diverse group, suggesting that t...

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“…12 This new technology is based on the finding that a synergistic effect occurs between GFs and a specific ECM protein called vitronectin (VN). [13][14][15][16] This has led to the development of novel dimeric, trimeric, and multimeric growth-promoting complexes incorporating GFs, such as insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs), in conjunction with VN (VN:GF). Further, the addition of these complexes to defined media has been demonstrated to stimulate short-term migration and proliferation in a range of cells, including adult skin-and corneal-derived epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

“…Further, the addition of these complexes to defined media has been demonstrated to stimulate short-term migration and proliferation in a range of cells, including adult skin-and corneal-derived epithelial cells. 13,16 In addition, this technology has proved successful in removing serum from the serial expansion of Kc; however, there is a need for a feeder cell layer in the culture system. Moreover, the approach reported by Dawson et al still used serum in the initial isolation step and involved binding the ECM:GF complex to the culture dishes.…”

Section: Introductionmentioning

confidence: 99%

Development of Defined Media for the Serum-Free Expansion of Primary Keratinocytes and Human Embryonic Stem Cells

Richards

Leavesley

Topping

et al. 2008

Tissue Engineering Part C: Methods

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Primary keratinocyte (Kc) cells and human embryonic stem (hES) cells are routinely propagated on a mouse fibroblast feeder layer in media containing fetal bovine serum or other nondefined factors. One disadvantage of using these nondefined factors is that they may inadvertently contaminate the culture system with infectious agents; thus, there remains a need to develop safe culture conditions free from poorly defined and/or animal products. Our laboratory has discovered that growth factors (GFs) and vitronectin (VN) can bind to each other resulting in synergistic short-term functional effects in several cell types. The aim of the current study was to determine whether primary Kc and hES cells can be established and serially propagated serum-free using medium containing VN, insulin-like growth factor-I, and insulin-like growth factor binding protein-3 (VN:GF). Here we demonstrate that primary Kc cells can be isolated, established, serially propagated, and re-form an epidermal layer using the VN:GF combination. Additionally, cell proliferation studies indicate that the Kcs proliferate using the VN:GF combination at a rate comparable to cells grown using serum. Similarly, we verified that this VN:GF combination could be employed for the serial propagation of hES cells. Importantly, both the Kc and hES cells retain their undifferentiated phenotype when cultured using the VN:GF combinations as a serum-free medium for up to 4 passages for Kc and at least 10 passages for hES cells as indicated by the expression of a range of cell surface markers. This study demonstrates that the novel, fully defined VN:GF medium is a viable alternative to media containing serum and highlights the potential of this technology for generating therapeutically viable cells and tissues.

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Responses of keratinocytes to substrate-bound vitronectin:growth factor complexes

Cited by 34 publications

References 50 publications

The Effect of Nano-Scale Topography on Keratinocyte Phenotype and Wound Healing Following Burn Injury

The Effect of Nano-Scale Topography on Keratinocyte Phenotype and Wound Healing Following Burn Injury

A Shared Mechanism of Adhesion Modulation for Tenascin-C and Fibulin-1

Development of Defined Media for the Serum-Free Expansion of Primary Keratinocytes and Human Embryonic Stem Cells

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