Modélisation de l'épithélium bronchique humain par la technologie des cellules souches pluripotentes induites (iPS)

Abstract : Pluripotent stem cells (PSC) include embryonic stem cells (ES) and induced pluripotent stem cells (iPS). They are defined by two fundamental properties: self-renewal and the capacity to differentiate into all cell types. ES cells are derived from the inner cell mass of embryos. They arouse the interest of the scientific community in particular for their ability to generate all tissues. They provide major therapeutic and pharmacological applications, including regenerative medicine, in vitro modelling of human diseases and molecular screening. However, the use of human blastocysts to generate ES cells raises many ethical problems. iPS circumvent these ethical issues as they can be derived from differentiated somatic tissues. Indeed, S. Yamanaka, Nobel Prize in 2012, discovered in 2006 a simple technique of cellular reprogramming. The transient expression of four genes (OCT4, SOX2, c-MYC and KLF4) is sufficient to reprogram mouse fibroblasts into iPS. These iPS cells have the same morphology and the same properties than ES cells. The following year, S. Yamanaka applied successfully his cocktail to human fibroblasts to produce human iPS (hiPS). hiPS may also overcome immunological problems raised by the use of ES cell for cellular therapy, as hiPS can be derived from the patient to be treated. In addition, it is easier to model genetic diseases from hiPS than ES, because it is possible to choose the donor cells to reprogram according to its genotype. Finally, from a pharmacological point of view, hiPS can provide a broad platform of molecular screening to treat various diseases. The aim of my research project is to use the hiPS technology to model the development of bronchial epithelium. First, in vivo, teratomas were formed by the injection of hiPS into immunodeficient mice. Teratomas highlight the ability of differentiation of our hiPS into bronchial epithelium. Second, in vitro, reproducing embryonic and foetal bronchial development provides a way to model bronchial epithelium in a dish.These techniques open the door to many potential research avenues from screening small molecules to engineering stem cells to repair bronchial epithelium, and will in fine promote new pharmacologic or cell-based treatments for respiratory diseases.
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Caroline Sansac. Modélisation de l'épithélium bronchique humain par la technologie des cellules souches pluripotentes induites (iPS). Médecine humaine et pathologie. Université Montpellier, 2016. Français. ⟨NNT : 2016MONTT014⟩. ⟨tel-01510250⟩

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