Defended by Karim OUDINA on 09-2015


Bone tissue engineering couples osteocompetent stem tells to an osteoconductive biomaterial in order to repair bone lesions. Despite proof of concept of the therapeutic interest of this association, tissue engineering constructs (TEC) have proven to be less effective than bone autograft. Cell component may be a limiting factor due to either premature death of transplanted tells or poor inherent osteogenic potential. This thesis is a contribution to the understanding of the role of the cellular component in the efficacy of TEC: one technologie part aiming to validate bioluminescence imaging to in vivo tracking of tell fate and one cognitive part which objective is to contribute to elucidate the fate and the role of human induced-pluripotent stem tells (h-iPSCm) within the context of bone tissue engineering. In a first part, we explored the possibility of using in vivo bioluminescence to track murine luciferase-transduced tells seeded either on calcium carbonate materials or on acrylonitrile-sodium-methallyl-sulfonate polymer. The photon flux emitted by the implanted tells revealed to be proportional to the number living tells, which permitted non-destructive tell quantification in vivo. In a second part, we evaluated the osteogenic potential of h-iPSCm and their derived-cells (MSC_h-iPSCm). Although MSC_h-iPSCm were not capable of bone differentiation in vitro or osteogenesis in vivo, h-iPSCm differentiated in bone tells in vitro and induced bone tissue formation in vivo, despite premature mortality. In vitro studies based on h-iPSCm conditioned-media analysis suggested that they were active through a paracrine way by secreting BMP-2, among other factors.

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