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Conception de biomatériaux hybrides à base de cellules souches pour l’ingénierie tissulaire

Abstract : Musculoskeletal conditions affecting bones and joints remain a challenge for regenerative medicine. The difficulties found are related to the needs of an optimal tissue vascularization for bone substitutes and to obtain a cartilage of quality for articular substitutes. The objectives of this PhD work were to differentiate human umbilical mesenchymal stem cells (MSC) - a tool of choice in regenerative medicine - towards a vascular phenotype and a joint chondrogenic phenotype to meet the needs of musculoskeletal tissue engineering. The differentiation of umbilical MSC into vascular smooth muscle cells was shown after 12 days of stimulation by soluble factors such as transforming growth factor (TGF)-beta1 and ascorbic acid. Facing the limits of two-dimensional culture supports in vitro, a three-dimensional culture model was set up using MSC cultured in pellets with or whitout an umbilical extracellular matrix (ECM) solution for the following experiences. Soluble factors have a limited efficacy and are often expensive, a transduction of MSC pellets was performed using recombinant adeno-associated viruses (rAAV) allowing a long term synthesis of factors by the cells. Here, the pellets were transduced using rAAV containing the Sox9 transcription factor gene to induce articular chondrogenic differentiation. This work demonstrates the interest of associating ECM and human umbilical MSC in a three-dimensional culture model, as well as gene therapy tools such as rAAVs to provide grafts that can be used to regenerate musculoskeletal tissues
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Benjamin Mesure. Conception de biomatériaux hybrides à base de cellules souches pour l’ingénierie tissulaire. Ingénierie biomédicale. Université de Lorraine; Universität des Saarlandes, 2018. Français. ⟨NNT : 2018LORR0189⟩. ⟨tel-01984493⟩

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