References of "Geris, Liesbet"
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See detailTo heal or not to heal: a multiscale model of the influence of oxygen during bone fracture healing.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Poster (2012, October 24)

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See detailA multiscale model of sprouting angiogenesis during fracture healing.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Conference (2012, September 18)

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See detailA Dynamic Graph Model of Endochondral Ossification can assess the Importance of Biological Actors in Differentiation
Kerkhofs, Johan ULg; Van Oosterwyck, Hans; Geris, Liesbet ULg

Conference (2012, September 18)

Cell-based tissue engineering constructs are a promising avenue for the treatment of long bone defects since they provide the primordial ingredients for bone regeneration. The construct provides the ... [more ▼]

Cell-based tissue engineering constructs are a promising avenue for the treatment of long bone defects since they provide the primordial ingredients for bone regeneration. The construct provides the appropriate micro-environment through the carrier, cells to form tissue and chemical cues to kick start the natural bone forming process. Clearly this approach will benefit from a more comprehensive appreciation of how cell populations and the microenvironment provided by the carrier can impact on bone formation in all its complexities. A cornucopia of studies of developmental biology have revealed many biological actors that together form a central network that orchestrates cell behaviour during this process and assures its robustness. This knowledge can be brought to bear specifically in the form of a mathematical model of endochondral ossification, the dominant type of ossification. This model can facilitate the understanding of how growth factors and transcription factors influence cell fate decisions and consequently answer the question whether they can boost bone healing. The model formalism accommodates the qualitative information that is typically available in developmental studies. The network comprises 46 nodes and 161 interactions, shown to be important in endochondral ossification. To simulate network dynamics in discrete time the normalized value of each gene is determined by additive functions where all interactions are assumed to be equally powerful. Furthermore, each species is represented by a fast variable (activity level, as determined by post translation modifications) which is assumed to be in equilibrium with a slow variable (mRNA) at all times. Through a Monte Carlo approach the importance of each node in the stability of chondrocytic phenotypes (proliferating, hypertrophic) is assessed. The hypertrophic state, driven by Runx2, is more stable than the proliferating chondrocyte. This higher stability seems to be conferred by faster reactions that favor the hypertrophic phenotype. In addition, the results point out that some transcription factors are necessary for the induction of a certain phenotype, whereas other transcription factors are required to maintain the phenotype, but are not necessary capable of inducing it. Overall, the model allows the importance of several important factors in the fate decision of mesenchymal cells to be quantitatively assessed based mainly on topological information. [less ▲]

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See detailMultiscale modeling of in the influence of oxygen during bone fracture healing.
Carlier, Aurélie ULg; Van Gastel, Nick; Carmeliet, Geert et al

Poster (2012, September 17)

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See detailMultiscale modeling of sprouting angiogenesis: tip cells are selected for the top.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Poster (2012, September 05)

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See detailMathematical Level-Set Modelling of Cell Growth on 3D Surfaces
Guyot, Yann ULg; Papatoniou, Ioannis; Chai, Yoke Chin et al

Poster (2012, September)

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See detailMultiscale modelling of the influence of VEGF on sprouting angiogenesis.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Poster (2012, July 06)

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See detailBridging the Gap: A Theoretical Model of Mechanotransduction Through ERK Signalling
Kerkhofs, Johan ULg; Geris, Liesbet ULg; Bosmans, Bart et al

Conference (2012, July 02)

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See detailTip cells at the top: a multiscale model of sprouting angiogenesis.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Conference (2012, July 01)

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See detailRelating the Chondrocyte Gene Network to Growth Plate Morphology: From Genes to Phenotype
Kerkhofs, Johan ULg; Roberts, Scott J; Luyten, Frank P et al

in PLoS ONE (2012)

During endochondral ossification, chondrocyte growth and differentiation is controlled by many local signalling pathways. Due to crosstalks and feedback mechanisms, these interwoven pathways display a ... [more ▼]

During endochondral ossification, chondrocyte growth and differentiation is controlled by many local signalling pathways. Due to crosstalks and feedback mechanisms, these interwoven pathways display a network like structure. In this study, a large-scale literature based logical model of the growth plate network was developed. The network is able to capture the different states (resting, proliferating and hypertrophic) that chondrocytes go through as they progress within the growth plate. In a first corroboration step, the effect of mutations in various signalling pathways of the growth plate network was investigated. [less ▲]

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See detailCoupling Cell Mechanics and Intracellular Signalling: Mechanotransduction through ERK
Kerkhofs, Johan ULg; Geris, Liesbet ULg; Bosmans, Bart et al

in Middleton, John (Ed.) The Proceedings of the 10th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering. Hotel Berlin, Berlin, Germany, April 7th – 11th, 2012 pages:0-0 (2012, April 12)

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See detailTip cells at the top: multiscale modeling of angiogenesis during fracture healing
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

in Computer Methods in Biomechanics and Biomedical Engineering (CMBBE) - Proceedings (2012, April)

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See detailA visco-elastic model for the prediction of orthodontic tooth movement.
Van Schepdael, An ULg; De Bondt, Kris; Geris, Liesbet ULg et al

in Computer Methods in Biomechanics & Biomedical Engineering (2012)

This study presents a biomechanical model of orthodontic tooth movement. Although such models have already been presented in the literature, most of them incorporate computationally expensive finite ... [more ▼]

This study presents a biomechanical model of orthodontic tooth movement. Although such models have already been presented in the literature, most of them incorporate computationally expensive finite elements (FE) methods to determine the strain distribution in the periodontal ligament (PDL). In contrast, the biomechanical model presented in this work avoids the use of FE methods. The elastic deformation of the PDL is modelled using an analytical approach, which does not require setting up a 3D model of the tooth. The duration of the lag phase is estimated using the calculated hydrostatic stresses, and bone remodelling is predicted by modelling the alveolar bone as a viscous material. To evaluate the model, some typically used motion patterns were simulated and a sensitivity analysis was carried out on the parameters. Results show that despite some shortcomings, the model is able to describe commonly used motion patterns in orthodontic tooth movement, in both single- and multi-rooted teeth. [less ▲]

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See detailMOSAIC: a multiscale model of osteogenesis and sprouting angiogenesis with lateral inhibition of endothelial cells.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Bentley, Katie et al

in PLoS Computational Biology (2012), 8(10), 1002724

The healing of a fracture depends largely on the development of a new blood vessel network (angiogenesis) in the callus. During angiogenesis tip cells lead the developing sprout in response to ... [more ▼]

The healing of a fracture depends largely on the development of a new blood vessel network (angiogenesis) in the callus. During angiogenesis tip cells lead the developing sprout in response to extracellular signals, amongst which vascular endothelial growth factor (VEGF) is critical. In order to ensure a correct development of the vasculature, the balance between stalk and tip cell phenotypes must be tightly controlled, which is primarily achieved by the Dll4-Notch1 signaling pathway. This study presents a novel multiscale model of osteogenesis and sprouting angiogenesis, incorporating lateral inhibition of endothelial cells (further denoted MOSAIC model) through Dll4-Notch1 signaling, and applies it to fracture healing. The MOSAIC model correctly predicted the bone regeneration process and recapitulated many experimentally observed aspects of tip cell selection: the salt and pepper pattern seen for cell fates, an increased tip cell density due to the loss of Dll4 and an excessive number of tip cells in high VEGF environments. When VEGF concentration was even further increased, the MOSAIC model predicted the absence of a vascular network and fracture healing, thereby leading to a non-union, which is a direct consequence of the mutual inhibition of neighboring cells through Dll4-Notch1 signaling. This result was not retrieved for a more phenomenological model that only considers extracellular signals for tip cell migration, which illustrates the importance of implementing the actual signaling pathway rather than phenomenological rules. Finally, the MOSAIC model demonstrated the importance of a proper criterion for tip cell selection and the need for experimental data to further explore this. In conclusion, this study demonstrates that the MOSAIC model creates enhanced capabilities for investigating the influence of molecular mechanisms on angiogenesis and its relation to bone formation in a more mechanistic way and across different time and spatial scales. [less ▲]

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See detailMechanisms of ectopic bone formation by human osteoprogenitor cells on CaP biomaterial carriers.
Chai, Y. C.; Roberts, S. J.; Desmet, E. et al

in Biomaterials (2012)

Stem cell-based strategies for bone regeneration, which use calcium phosphate (CaP)-based biomaterials in combination with developmentally relevant progenitor populations, have significant potential for ... [more ▼]

Stem cell-based strategies for bone regeneration, which use calcium phosphate (CaP)-based biomaterials in combination with developmentally relevant progenitor populations, have significant potential for clinical repair of skeletal defects. However, the exact mechanism of action and the stem cell-host-material interactions are still poorly understood. We studied if pre-conditioning of human periosteum-derived cells (hPDCs) in vitro could enhance, in combination with a CaP-based biomaterial carrier, ectopic bone formation in vivo. By culturing hPDCs in a biomimetic calcium (Ca(2+)) and phosphate (P(i)) enriched culture conditions, we observed an enhanced cell proliferation, decreased expression of mesenchymal stem cell (MSC) markers and upregulation of osteogenic genes including osterix, Runx2, osteocalcin, osteopontin, and BMP-2. However, the in vitro pre-conditioning protocols were non-predictive for in vivo ectopic bone formation. Surprisingly, culturing in the presence of Ca(2+) and P(i) supplements resulted in partial or complete abrogation of in vivo ectopic bone formation. Through histological, immunohistochemical and microfocus X-ray computed tomography (muCT) analysis of the explants, we found that in situ proliferation, collagen matrix deposition and the mediation of osteoclastic activity by hPDCs are associated to their ectopic bone forming capacity. These data were validated by the multivariate analysis and partial least square regression modelling confirming the non-predictability of in vitro parameters on in vivo ectopic bone formation. Our series of experiments provided further insights on the stem cell-host-material interactions that govern in vivo ectopic bone induction driven by hPDCs on CaP-based biomaterials. [less ▲]

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See detailCurrent views on calcium phosphate osteogenicity and the translation into effective bone regeneration strategies.
Chai, Y. C.; Carlier, Aurélie ULg; Bolander, J. et al

in Acta Biomaterialia (2012), 8(11), 3876-87

Calcium phosphate (CaP) has traditionally been used for the repair of bone defects because of its strong resemblance to the inorganic phase of bone matrix. Nowadays, a variety of natural or synthetic CaP ... [more ▼]

Calcium phosphate (CaP) has traditionally been used for the repair of bone defects because of its strong resemblance to the inorganic phase of bone matrix. Nowadays, a variety of natural or synthetic CaP-based biomaterials are produced and have been extensively used for dental and orthopaedic applications. This is justified by their biocompatibility, osteoconductivity and osteoinductivity (i.e. the intrinsic material property that initiates de novo bone formation), which are attributed to the chemical composition, surface topography, macro/microporosity and the dissolution kinetics. However, the exact molecular mechanism of action is unknown. This review paper first summarizes the most important aspects of bone biology in relation to CaP and the mechanisms of bone matrix mineralization. This is followed by the research findings on the effects of calcium (Ca(2)(+)) and phosphate (PO(4)(3)(-)) ions on the migration, proliferation and differentiation of osteoblasts during in vivo bone formation and in vitro culture conditions. Further, the rationale of using CaP for bone regeneration is explained, focusing thereby specifically on the material's osteoinductive properties. Examples of different material forms and production techniques are given, with the emphasis on the state-of-the art in fine-tuning the physicochemical properties of CaP-based biomaterials for improved bone induction and the use of CaP as a delivery system for bone morphogenetic proteins. The use of computational models to simulate the CaP-driven osteogenesis is introduced as part of a bone tissue engineering strategy in order to facilitate the understanding of cell-material interactions and to gain further insight into the design and optimization of CaP-based bone reparative units. Finally, limitations and possible solutions related to current experimental and computational techniques are discussed. [less ▲]

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See detailThe Effect of Activating Fibroblast Growth Factor Receptor 3 Mutations on Osteogenic Differentiation and Ectopic Bone Formation by Human Periosteal Derived Cells
Bolander, Johanna; Roberts, Scott; Eyckmans, jeroen et al

in Journal of Tissue Science & Engineering (2012), 2

Activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) have previously been shown to cause skeletal dysplasias through their effect on growth plate chondrocytes. However, the effect of FGFR3 ... [more ▼]

Activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) have previously been shown to cause skeletal dysplasias through their effect on growth plate chondrocytes. However, the effect of FGFR3 mutations on bone progenitor cells may differ. The objective of this study was to investigate the effect of specific activating FGFR3 mutations on ectopic in vivo bone formation by periosteal derived cells (PDCs) seeded on calcium phosphate/ collagen scaffolds. PDCs were isolated from hypochondroplasic (N540K mutation) and achondroplasic (G380R mutation) patients, along with age/sex matched controls. These cells were characterised in vitro for proliferation, osteogenic differentiation, FGFR3 signalling and in vivo bone formation. Subsequently, empirical modelling was used to find correlations between in vivo formed bone and in vitro cell behaviour. These data showed that in contrast to the G380R mutation, which produced no bone, the N540K mutation induced significant ectopic bone formation on specific carriers. This allowed correlation between percentage of induced bone formation to elevated in vitro proliferation and differentiation. Correlating osteogenic markers included Collagen type 1, alkaline phosphatase and osteocalcin. Enhanced proliferation was attributed to increased phosphorylation of Erk-1/2. This study highlights the importance of FGFR3 in periosteal cell differentiation and also indicates it potential for targeted tissue engineering strategies. [less ▲]

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See detailA mathematical model of adult subventricular neurogenesis.
Ashbourn, JM; Miller, JJ; Reumers, V et al

in Journal of the Royal Society, Interface (2012)

Neurogenesis has been the subject of active research in recent years and many authors have explored the phenomenology of the process, its regulation and its purported purpose. Recent developments in ... [more ▼]

Neurogenesis has been the subject of active research in recent years and many authors have explored the phenomenology of the process, its regulation and its purported purpose. Recent developments in bioluminescent imaging (BLI) allow direct in vivo imaging of neurogenesis, and in order to interpret the experimental results, mathematical models are necessary. This study proposes such a mathematical model that describes adult mammalian neurogenesis occurring in the subventricular zone and the subsequent migration of cells through the rostral migratory stream to the olfactory bulb (OB). This model assumes that a single chemoattractant is responsible for cell migration, secreted both by the OB and in an endocrine fashion by the cells involved in neurogenesis. The solutions to the system of partial differential equations are compared with the physiological rodent process, as previously documented in the literature and quantified through the use of BLI, and a parameter space is described, the corresponding solution to which matches that of the rodent model. A sensitivity analysis shows that this parameter space is stable to perturbation and furthermore that the system as a whole is sloppy. A large number of parameter sets are stochastically generated, and it is found that parameter spaces corresponding to physiologically plausible solutions generally obey constraints similar to the conditions reported in vivo. This further corroborates the model and its underlying assumptions based on the current understanding of the investigated phenomenon. Concomitantly, this leaves room for further quantitative predictions pertinent to the design of future proposed experiments. [less ▲]

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See detailMultiscale modeling of sprouting angiogenesis
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Poster (2011, December 02)

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See detailCalcium phosphate scaffolds customizations for bone tissue engineering applications
Carlier, Aurélie ULg; Chai, Yoke Chin; Theys, Tina et al

Poster (2011, November 18)

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