Synthèse de surfaces bioactives pour le contrôle de la différenciation de cellules souches

par Emilie Prouve

Projet de thèse en Physico-Chimie de la Matière Condensée

Sous la direction de Marie-Christine Durrieu et de Gaétan Laroche.

Thèses en préparation à Bordeaux en cotutelle avec l'Université Laval , dans le cadre de École doctorale des sciences chimiques (Talence, Gironde) , en partenariat avec Chimie et Biologie des Membranes et des Nanoobjets (Bordeaux) (laboratoire) et de Equipe de Recherche 3Bio's : Surfaces Bioactives, Biomatériaux et produits de l'Ingéniérie Tissulaire Biomimétique. (equipe de recherche) depuis le 28-09-2017 .


  • Résumé

    The study of Mesenchymal Stem Cells (MSC) has raised the hope of a cell-based therapy for autoimmune diseases and for tissue engineering due to their high availability based on self-renewal and their high capability of differentiation into mesodermal derivatives. Identification of factors that maintain their stemness properties, monitor and control MSC differentiation is crucial. Cells evolve following nanoscale physical and chemical signals they receive from ExtraCellular Matrix (ECM). The challenge lies in synthesizing materials able to reproduce these processes. The objective of this PhD research is to create new micro-, nano-patterned surfaces able to maintain MSC in their stem state or to allow their selective differentiation. This is of particular importance in the field of stem cells for which the controlled differentiation protocols toward specific lineages has to be improved for their use in tissue engineering. In this context, nanotechnologies undeniably represent excellent tools for producing structured materials that can mimic the ECM and lead to bioactivity. Over the last decade, extreme miniaturization of micro- and nano-systems has originated actual revolutions in life sciences and their health applications. In parallel, important advances have been made over the past few years in the field of biomaterials, and most of these have been associated with rendering materials biologically active. It is well known that, when presented with appropriate biological cues, cell receptors will bind to signaling biomolecules and transmit information by activating signaling cascades which then modulate gene expression and determine important cell fate processes such as differentiation. With the recent advances in nanotechnology, the submicron-scale spatial patterning of extracellular signaling molecules has become within reach and powerful tools for investigating the optimal condition for cell-biomaterial communication and inducing desired cell behaviors. For this project, we will focus (i) on the design, synthesis and elaboration of controllable micro-, nano-structured materials, entitled Smart Synthetic ExtraCellular Matrices (SS-ECM) and (ii) on the surface functionalization of materials with various active principles [cell adhesion peptides, cell differentiation peptides]) to reproduce the role of signaling biomolecules. The final objective (iii) is to evaluate the influence of these micro-, nano-structured materials (functionalized or not) on stem cell fate and behavior of in vitro commercialized MSC and generated iPS-derived MSC such as their biological properties in term of phenotype, function, immunomodulation and differentiation into mature specialized cells (adipocytes, chondrocytes and osteoblasts). Human iPS cells are in vitro generated pluripotent stem cells with equivalent behavior as human embryonic stem cells (whose use is largely restricted by ethical issues). They can serve as an unlimited source of cells for further clinical applications. In this regard, MSC can be derived in vitro from iPS cells that therefore appear to be a new potential candidate for unlimited source of MSC.

  • Titre traduit

    Synthesis of bioactive surfaces for the control of stem cell differentiation


  • Résumé

    The study of Mesenchymal Stem Cells (MSC) has raised the hope of a cell-based therapy for autoimmune diseases and for tissue engineering due to their high availability based on self-renewal and their high capability of differentiation into mesodermal derivatives. Identification of factors that maintain their stemness properties, monitor and control MSC differentiation is crucial. Cells evolve following nanoscale physical and chemical signals they receive from ExtraCellular Matrix (ECM). The challenge lies in synthesizing materials able to reproduce these processes. The objective of this PhD research is to create new micro-, nano-patterned surfaces able to maintain MSC in their stem state or to allow their selective differentiation. This is of particular importance in the field of stem cells for which the controlled differentiation protocols toward specific lineages has to be improved for their use in tissue engineering. In this context, nanotechnologies undeniably represent excellent tools for producing structured materials that can mimic the ECM and lead to bioactivity. Over the last decade, extreme miniaturization of micro- and nano-systems has originated actual revolutions in life sciences and their health applications. In parallel, important advances have been made over the past few years in the field of biomaterials, and most of these have been associated with rendering materials biologically active. It is well known that, when presented with appropriate biological cues, cell receptors will bind to signaling biomolecules and transmit information by activating signaling cascades which then modulate gene expression and determine important cell fate processes such as differentiation. With the recent advances in nanotechnology, the submicron-scale spatial patterning of extracellular signaling molecules has become within reach and powerful tools for investigating the optimal condition for cell-biomaterial communication and inducing desired cell behaviors. For this project, we will focus (i) on the design, synthesis and elaboration of controllable micro-, nano-structured materials, entitled Smart Synthetic ExtraCellular Matrices (SS-ECM) and (ii) on the surface functionalization of materials with various active principles [cell adhesion peptides, cell differentiation peptides]) to reproduce the role of signaling biomolecules. The final objective (iii) is to evaluate the influence of these micro-, nano-structured materials (functionalized or not) on stem cell fate and behavior of in vitro commercialized MSC and generated iPS-derived MSC such as their biological properties in term of phenotype, function, immunomodulation and differentiation into mature specialized cells (adipocytes, chondrocytes and osteoblasts). Human iPS cells are in vitro generated pluripotent stem cells with equivalent behavior as human embryonic stem cells (whose use is largely restricted by ethical issues). They can serve as an unlimited source of cells for further clinical applications. In this regard, MSC can be derived in vitro from iPS cells that therefore appear to be a new potential candidate for unlimited source of MSC.