References of "Geris, Liesbet"
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See detailComputational Modeling of a Growing Fetal Long Bone
Nazemi, Sayed Majid ULiege; Geris, Liesbet ULiege

in ESB 2019 Book of Abstracts (in press)

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See detailDigital twins in tissue engineering: from bench to bedside via the computer.
Geris, Liesbet ULiege

in Abstract book of CMBBE2019 (2019)

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See detailUncoupling of in-vitro identity of embryonic limb derived skeletal progenitors and their in-vivo bone forming potential
Verbeeck, L.; Geris, Liesbet ULiege; Tylzanowski, P. et al

in Scientific Reports (2019), 9(1),

The healing of large bone defects remains a major unmet medical need. Our developmental engineering approach consists of the in vitro manufacturing of a living cartilage tissue construct that upon ... [more ▼]

The healing of large bone defects remains a major unmet medical need. Our developmental engineering approach consists of the in vitro manufacturing of a living cartilage tissue construct that upon implantation forms bone by recapitulating an endochondral ossification process. Key to this strategy is the identification of the cells to produce such cartilage intermediates efficiently. We applied a cell selection strategy based on published skeletal stem cell markers using mouse embryonic limb cartilage as cell source and analysed their potential to form bone in an in vivo ectopic assay. FGF2 supplementation to the culture media for expansion blocked dedifferentiation of the embryonic cartilage cells in culture and enriched for stem cells and progenitors as quantified using the recently published CD marker set. However, when the stem cells and progenitors were fractionated from expanded embryonic cartilage cells and assessed in the ectopic assay, a major loss of bone forming potential was observed. We conclude that cell expansion appears to affect the association between cell identity based on CD markers and in vivo bone forming capacity. © 2019, The Author(s). [less ▲]

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See detailThe Third Era of Tissue Engineering: Reversing the Innovation Drivers.
Geris, Liesbet ULiege; Papantoniou, Ioannis

in Tissue engineering. Part A (2019), 25(11-12), 821-826

IMPACT STATEMENT: From this perspective, we discuss the different stages of development the tissue engineering (TE) field has gone through in its relatively young history. We discuss how TE is evolving ... [more ▼]

IMPACT STATEMENT: From this perspective, we discuss the different stages of development the tissue engineering (TE) field has gone through in its relatively young history. We discuss how TE is evolving from a technology-driven, science-focused field toward a patient-driven, manufacturing-focused one where patients' needs are translated into production process requirements, and subsequently into technological and biological innovations needed to meet the regulatory and clinical demands. [less ▲]

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See detailNeurofibromatosis type 1-related pseudarthrosis: Beyond the pseudarthrosis site.
Brekelmans, Carlijn; Hollants, Silke; De Groote, Caroline et al

in Human Mutation (2019)

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting approximately 1 in 2,000 newborns. Up to 5% of NF1 patients suffer from pseudarthrosis of a long bone (NF1-PA). Current ... [more ▼]

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting approximately 1 in 2,000 newborns. Up to 5% of NF1 patients suffer from pseudarthrosis of a long bone (NF1-PA). Current treatments are often unsatisfactory, potentially leading to amputation. To gain more insight into the pathogenesis we cultured cells from PA tissue and normal-appearing periosteum of the affected bone for NF1 mutation analysis. PA cells were available from 13 individuals with NF1. Biallelic NF1 inactivation was identified in all investigated PA cells obtained during the first surgery. Three of five cases sampled during a later intervention showed biallelic NF1 inactivation. Also, in three individuals, we examined periosteum-derived cells from normal-appearing periosteum proximal and distal to the PA. We identified the same biallelic NF1 inactivation in the periosteal cells outside the PA region. These results indicate that NF1 inactivation is required but not sufficient for the development of NF1-PA. We observed that late-onset NF1-PA occurs and is not always preceded by congenital bowing. Furthermore, the failure to identify biallelic inactivation in two of five later interventions and one reintervention with a known somatic mutation indicates that NF1-PA can persist after the removal of most NF1 negative cells. [less ▲]

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See detailTowards Self-Regulated Bioprocessing: A Compact Benchtop Bioreactor System for Monitored and Controlled 3D Cell and Tissue Culture.
de Bournonville, Sebastien; Lambrechts, Toon; Vanhulst, Johan et al

in Biotechnology Journal (2019)

Bioreactors are crucial tools for the manufacturing of living cell-based tissue engineered products. However, to reach the market successfully, higher degrees of automation, as well as a decreased ... [more ▼]

Bioreactors are crucial tools for the manufacturing of living cell-based tissue engineered products. However, to reach the market successfully, higher degrees of automation, as well as a decreased footprint still need to be reached. In this study, the use of a benchtop bioreactor for in vitro perfusion culture of scaffold-based tissue engineering constructs is assessed. A low-footprint benchtop bioreactor system is designed, comprising a single-use fluidic components and a bioreactor housing. The bioreactor is operated using an in-house developed program and the culture environment is monitored by specifically designed sensor ports. A gas-exchange module is incorporated allowing for heat and mass transfers. Titanium-based scaffolds are seeded with human periosteum-derived cells and cultured up to 3 weeks. The benchtop bioreactor constructs are compared to benchmark perfusion systems. Live/Dead stainings, DNA quantifications, glucose consumption, and lactate production assays confirm that the constructs cultured in the benchtop bioreactor grew similarly to the benchmark systems. Manual regulation of the system set points enabled efficient alteration of the culture environment in terms of temperature, pH, and dissolved oxygen. This study provides the necessary basis for the development of low-footprint, automated, benchtop perfusion bioreactors and enables the implementation of active environment control. [less ▲]

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See detailHuman Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture.
Gupta, Priyanka; Hall, Gabriella Nilsson; Geris, Liesbet ULiege et al

in Stem Cells Translational Medicine (2019)

Xenogeneic-free media are required for translating advanced therapeutic medicinal products to the clinics. In addition, process efficiency is crucial for ensuring cost efficiency, especially when ... [more ▼]

Xenogeneic-free media are required for translating advanced therapeutic medicinal products to the clinics. In addition, process efficiency is crucial for ensuring cost efficiency, especially when considering large-scale production of mesenchymal stem cells (MSCs). Human platelet lysate (HPL) has been increasingly adopted as an alternative for fetal bovine serum (FBS) for MSCs. However, its therapeutic and regenerative potential in vivo is largely unexplored. Herein, we compare the effects of FBS and HPL supplementation for a scalable, microcarrier-based dynamic expansion of human periosteum-derived cells (hPDCs) while assessing their bone forming capacity by subcutaneous implantation in small animal model. We observed that HPL resulted in faster cell proliferation with a total fold increase of 5.2 +/- 0.61 in comparison to 2.7 +/- 02.22-fold in FBS. Cell viability and trilineage differentiation capability were maintained by HPL, although a suppression of adipogenic differentiation potential was observed. Differences in mRNA expression profiles were also observed between the two on several markers. When implanted, we observed a significant difference between the bone forming capacity of cells expanded in FBS and HPL, with HPL supplementation resulting in almost three times more mineralized tissue within calcium phosphate scaffolds. FBS-expanded cells resulted in a fibrous tissue structure, whereas HPL resulted in mineralized tissue formation, which can be classified as newly formed bone, verified by muCT and histological analysis. We also observed the presence of blood vessels in our explants. In conclusion, we suggest that replacing FBS with HPL in bioreactor-based expansion of hPDCs is an optimal solution that increases expansion efficiency along with promoting bone forming capacity of these cells. Stem Cells Translational Medicine 2019. [less ▲]

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See detailAnalyzing the influence of driving physico-chemical characteristics in intra-oral bone regeneration using a predictive empirical model
Sadeghian Dehkord, Ehsan ULiege; Kerckhofs, Greet; Lambert, France et al

Conference (2018, November 30)

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See detailDeveloping a predictive empirical model to optimize biomaterials characteristics for intra-oral bone regeneration
Sadeghian Dehkord, Ehsan ULiege; Kerckhofs, Greet; Lambert, France ULiege et al

Scientific conference (2018, September 11)

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See detailUnderstanding the interactions between Wnt and BMP signaling pathways in human Periosteum Derived Cells
Germain, Morgan ULiege; Bolander, Johanna; Geris, Liesbet ULiege

Conference (2018, September 07)

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See detailComputational modelling of the effect of growth factors on human mesenchymal stem cell proliferation in 3D porous scaffolds
Mehrian, Mohammad ULiege; Papantoniou, Ioannis; Lambrechts, Toon et al

in Proceedings of the Virtual Physiological Human conference (VPH), Zaragoza, Spain, 5-7 September 2018 (2018, September 05)

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See detailThe future is digital: In silico tissue engineering
Geris, Liesbet ULiege; Lambrechts, Toon; Carlier, Aurélie et al

in Current Opinion in Biomedical Engineering (2018), 6

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See detailComputational modelling of human mesenchymal stem cell proliferation and extra cellular matrix production in 3D porous scaffolds in a perfusion bioreactor
Mehrian, Mohammad ULiege; Papantoniou, Ioannis; Lambrechts, Toon et al

in Proceedings of the 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering (CMBBE) (2018, March 26)

3D porous scaffolds are frequently used in tissue engineering (TE) applications in combination with bioreactor systems because of their ability to induce reproducible culture conditions that can control ... [more ▼]

3D porous scaffolds are frequently used in tissue engineering (TE) applications in combination with bioreactor systems because of their ability to induce reproducible culture conditions that can control specific cell behavior such as proliferation and extracellular matrix (ECM) production. A computational model describing neotissue growth inside 3D scaffolds in a perfusion bioreactor was developed, with neotissue being considered the combination of cells and their extra cellular matrix. In the model, the speed of neotissue growth depends on the flow-induced shear stress, curvature and the local concentrations of oxygen, glucose and lactate. The goal of this study is to make a distinction between the cell and the ECM fraction within the neotissue in the model to allow for a more detailed validation and optimization of the process. [less ▲]

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See detailMulti-objective optimization of cost-efficient neotissue growth inside 3D scaffolds using evolutionary algorithms
Mehrian, Mohammad ULiege; olofsson, Simon; Misener, Ruth et al

in Proceedings of the 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering (CMBBE) (2018, March 26)

Tissue engineering is a fast progressing domain where solutions are provided for organ failure or tissue damage. Computer models can facilitate the design of optimal production process conditions leading ... [more ▼]

Tissue engineering is a fast progressing domain where solutions are provided for organ failure or tissue damage. Computer models can facilitate the design of optimal production process conditions leading to robust and economically viable products. We developed a computational model describing the neotissue growth (cells + their ECM) inside 3D scaffolds in a perfusion bioreactor. Here we apply multi-objective optimization (MOO) to maximize neotissue growth whilst minimizing the cost coming from medium refreshment and associated labor. [less ▲]

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See detailDeciphering the combined effect of bone morphogenetic protein 6 (BMP6) and calcium phosphate on bone formation capacity of periosteum derived cells-based tissue engineering constructs
Ji, W.; Kerckhofs, G.; Geeroms, C. et al

in Acta Biomaterialia (2018)

Cell based combination products with growth factors on optimal carriers represent a promising tissue engineering strategy to treat large bone defects. In this concept, bone morphogenetic protein (BMP) and ... [more ▼]

Cell based combination products with growth factors on optimal carriers represent a promising tissue engineering strategy to treat large bone defects. In this concept, bone morphogenetic protein (BMP) and calcium phosphate (CaP)-based scaffolds can act as potent components of the constructs to steer stem cell specification, differentiation and initiate subsequent in vivo bone formation. However, limited insight into BMP dosage and the cross-talk between BMP and CaP materials, hampers the optimization of in vivo bone formation and subsequent clinical translation. Herein, we combined human periosteum derived progenitor cells with different doses of BMP6 and with three types of clinical grade CaP-scaffolds (ChronOs® ReproBone™ & CopiOs®). Comprehensive cellular and molecular analysis was performed based on in vitro cell metabolic activity and signaling pathway activation, as well as in vivo ectopic bone forming capacity after 2 weeks and 5 weeks in nude mice. Our data showed that cells seeded on CaP scaffolds with an intermediate Ca2+ release rate combined with low or medium dosage of BMP6 demonstrated a robust new bone formation after 5 weeks, which was contributed by both donor and host cells. This phenomenon might be due to the delicate balance between Ca2+ and BMP pathways, allowing an appropriate activation of the canonical BMP signaling pathway that is required for in vivo bone formation. For high BMP6 dosage, we found that the BMP6 dosage overrides the effect of the Ca2+ release rate and this appeared to be a dominant factor for ectopic bone formation. Taken together, this study illustrates the importance of matching BMP dosage and CaP properties to allow an appropriate activation of canonical BMP signaling that is crucial for in vivo bone formation. It also provides insightful knowledge with regard to clinical translation of cell-based constructs for bone regeneration. Statement of Significance: The combination of bone morphogenetic proteins (BMP) and calcium phosphate (CaP)-based biomaterials with mesenchymal stromal cells represents a promising therapeutic strategy to treat large bone defects, an unmet medical need. However, there is limited insight into the optimization of these combination products, which hampers subsequent successful clinical translation. Our data reveal a delicate balance between Ca2+ and BMP pathways, allowing an appropriate activation of canonical BMP signaling required for in vivo bone formation. Our findings illustrate the importance of matching BMP dosage and CaP properties in the development of cell-based constructs for bone regeneration. © 2018 Acta Materialia Inc. [less ▲]

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See detailComputational Modeling and Reverse Engineering to Reveal Dominant Regulatory Interactions Controlling Osteochondral Differentiation: Potential for Regenerative Medicine.
Lesage, Raphaelle; Kerkhofs, Johan; Geris, Liesbet ULiege

in Frontiers in bioengineering and biotechnology (2018), 6

The specialization of cartilage cells, or chondrogenic differentiation, is an intricate and meticulously regulated process that plays a vital role in both bone formation and cartilage regeneration ... [more ▼]

The specialization of cartilage cells, or chondrogenic differentiation, is an intricate and meticulously regulated process that plays a vital role in both bone formation and cartilage regeneration. Understanding the molecular regulation of this process might help to identify key regulatory factors that can serve as potential therapeutic targets, or that might improve the development of qualitative and robust skeletal tissue engineering approaches. However, each gene involved in this process is influenced by a myriad of feedback mechanisms that keep its expression in a desirable range, making the prediction of what will happen if one of these genes defaults or is targeted with drugs, challenging. Computer modeling provides a tool to simulate this intricate interplay from a network perspective. This paper aims to give an overview of the current methodologies employed to analyze cell differentiation in the context of skeletal tissue engineering in general and osteochondral differentiation in particular. In network modeling, a network can either be derived from mechanisms and pathways that have been reported in the literature (knowledge-based approach) or it can be inferred directly from the data (data-driven approach). Combinatory approaches allow further optimization of the network. Once a network is established, several modeling technologies are available to interpret dynamically the relationships that have been put forward in the network graph (implication of the activation or inhibition of certain pathways on the evolution of the system over time) and to simulate the possible outcomes of the established network such as a given cell state. This review provides for each of the aforementioned steps (building, optimizing, and modeling the network) a brief theoretical perspective, followed by a concise overview of published works, focusing solely on applications related to cell fate decisions, cartilage differentiation and growth plate biology. Particular attention is paid to an in-house developed example of gene regulatory network modeling of growth plate chondrocyte differentiation as all the aforementioned steps can be illustrated. In summary, this paper discusses and explores a series of tools that form a first step toward a rigorous and systems-level modeling of osteochondral differentiation in the context of regenerative medicine. [less ▲]

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