Showing papers by "Paul Bourgine published in 2014"
TL;DR: The utility of engineered ECM-based devices as off-the-shelf regenerative niches capable of recruiting and instructing resident cells toward the formation of a specific tissue is supported.
Abstract: The role of cell-free extracellular matrix (ECM) in triggering tissue and organ regeneration has gained increased recognition, yet current approaches are predominantly based on the use of ECM from fully developed native tissues at nonhomologous sites. We describe a strategy to generate customized ECM, designed to activate endogenous regenerative programs by recapitulating tissue-specific developmental processes. The paradigm was exemplified in the context of the skeletal system by testing the osteoinductive capacity of engineered and devitalized hypertrophic cartilage, which is the primordial template for the development of most bones. ECM was engineered by inducing chondrogenesis of human mesenchymal stromal cells and devitalized by the implementation of a death-inducible genetic device, leading to cell apoptosis on activation and matrix protein preservation. The resulting hypertrophic cartilage ECM, tested in a stringent ectopic implantation model, efficiently remodeled to form de novo bone tissue of host origin, including mature vasculature and a hematopoietic compartment. Importantly, cartilage ECM could not generate frank bone tissue if devitalized by standard “freeze & thaw” (F&T) cycles, associated with a significant loss of glycosaminoglycans, mineral content, and ECM-bound cytokines critically involved in inflammatory, vascularization, and remodeling processes. These results support the utility of engineered ECM-based devices as off-the-shelf regenerative niches capable of recruiting and instructing resident cells toward the formation of a specific tissue.
62 citations
TL;DR: A method is reported to generate a hMSCs line with controlled survival, through the implementation of a pre-established suicide system (inducible caspase 9, iCasp9) in hTERT-transduced h MSCs, generated with defined properties and allowing for temporally controlled survival.
38 citations
TL;DR: This work designed an original methodological framework implemented in a software tool called Match-IT, which was used to construct an atlas composed of 6 gene expression templates from a cohort of zebrafish early embryos spanning 6 developmental stages from 4 to 6.3 hpf.
Abstract: A gene expression atlas is an essential resource to quantify and understand the multiscale processes of embryogenesis in time and space. The automated reconstruction of a prototypic 4D atlas for vertebrate early embryos, using multicolor fluorescence in situ hybridization with nuclear counterstain, requires dedicated computational strategies. To this goal, we designed an original methodological framework implemented in a software tool called Match-IT. With only minimal human supervision, our system is able to gather gene expression patterns observed in different analyzed embryos with phenotypic variability and map them onto a series of common 3D templates over time, creating a 4D atlas. This framework was used to construct an atlas composed of 6 gene expression templates from a cohort of zebrafish early embryos spanning 6 developmental stages from 4 to 6.3 hpf (hours post fertilization). They included 53 specimens, 181,415 detected cell nuclei and the segmentation of 98 gene expression patterns observed in 3D for 9 different genes. In addition, an interactive visualization software, Atlas-IT, was developed to inspect, supervise and analyze the atlas. Match-IT and Atlas-IT, including user manuals, representative datasets and video tutorials, are publicly and freely available online. We also propose computational methods and tools for the quantitative assessment of the gene expression templates at the cellular scale, with the identification, visualization and analysis of coexpression patterns, synexpression groups and their dynamics through developmental stages.
25 citations
TL;DR: This paper presents a meta-modelling framework for estimating the total number of components in a complex system and some of the components are simple, efficient, and Turing-complete.
Abstract: * Contact author. ** MLG, Departement dʼInformatique, Universite Libre de Bruxelles, Boulevard du Trio Vakgroep Computerwetenschappen, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brus † Computational Epidemiology Group, Department of Veterinary Sciences, University Grugliasco (TO), Italy; Complex Systems Unit, Molecular Biotechnology Center, Univers (TO), Italy; Applied Research on Computational Complex Systems, Department of C Svizzera 185, IT-10149 Torino, Italy. E-mail: mario.giacobini@unito.it ‡ IRIDIA, Universite Libre de Bruxelles, 50, Avenue Franklin Roosevelt, CP 194/6, B-10 (H.B.); mdorigo@ulb.ac.be (M.D.) § Complex Systems Institute, Paris Ile-de-France (ISC-PIF), CREA, CNRS, and Ecole Pol France. E-mail: paul.bourgine@polytechnique.edu (P.B.); rene.doursat@polytechnique.ed
3 citations
TL;DR: In this article, an agent-based model of biological "autopoiesis", the process by which a cell creates and continuously regenerates itself, considered one of the defining characteristics of life, is proposed.
Abstract: We propose an original 2D agent-based model of biological "autopoiesis," the process by which a cell creates and continuously regenerates itself, considered one of the defining characteristics of life. In the space of our simulations, the positions of free molecules are continuous, and polymerized membrane components are regularly arranged (plus noise). While autopoiesis commonly refers to the self-driven maintenance of a system, we also follow Varela's historical study of emergence, and show that the same model can account for both self-perpetuation and self-formation—a step toward uniting the three main perspectives on life: origins, autopoiesis, and replication. Exploring different initial and environmental conditions, we observe that destructive reactions are important for the survival of our autopoietic system, and evaluate their impact on its lifespan. The tendency of cells to form spurious outgrowths is counteracted by moderate decay of the membrane.
1 citations