The organs of the body are formed by cell division from stem cells. Differentiation of stem cells to the specific cell types of a given tissue or organ depends on the inductive signals that are secreted in the direct environment. Several families of secreted factors have been identified that induce cells to their specific fates. However, our understanding of the regulation of cell differentiation, one of the major themes of biology, is still very limited. The revolutionary discovery of embryonic stem cells (ES cells) provides an opportunity to investigate this in controlled conditions. The general aim of this research action is to identify culture conditions and inductive signals with which we can regulate and channel the proliferation and differentiation behavior of stem cells for in vitro development of pancreatic, muscle, and blood cells. After reintroduction of the differentiated ES cells into the body, the organ microenvironment may further induce their correct differentiation to mature functional tissues. This approach is expected to provide novel treatments for chronic and degenerative diseases, commonly referred to as replacement therapy or regenerative medicine. When this can be obtained, we will investigate the functional potential of the engineered cells (e.g. restoration of glucose homeostasis in diabetic animals) and their safety aspects (genomic and chromosomal stability, risk of cancer). Furthermore, the ethical aspect of this approach will be investigated. There are several important ethical issues associated with the application of human stem cells: the need for human embryo's for research and therapeutic applications, the fear for reproductive cloning of human beings, the possibility to modify the genetic content of human cells .
Another issue which is revolutionizing biomedical research is the discovery of stem cells and their plasticity in adult organs. For example, adult bone marrow can generate not only blood cells, but also muscle cell types. Stem cells retained in the brain can differentiate to form the cells of other organs, such as muscle, blood, gut, liver and heart. Recently it has been established that adults contain stem cells that can participate to the formation of multiple tissues when these cells are injected into an embryo. As in the case of ES cells, very little is known about the conditions which direct the growth and differentiation of adult stem cells.
This project aims at building knowledge and understanding of the biology of stem cells in view of a potential cell therapy approach. We will use a gain-of-function approach, the addition of secreted bioactive molecules, to analyze the role of these secreted factors on the growth and differentiation of stem cells in culture along a chosen path. The growth stimulation of the stem cells and their differentiation in specific cell types will be determined by several classical means (histology, immunodetection of markers, molecular probes). One new tool, PCR primer array for multiple stem, precursor and differentiated cell-types will be developed here to allow higher throughput and broader spectrum of analysis by Real-Time PCR.