| 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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