Recreation of functional bloodvessels and supporting structures by stimulating stem cells and vascular stem structures via gene therapy

The main issue is to understand the biology of bloodvessels and their role in tumor formation and fibrosis. Fibrosis is a common denominator in a wide variety of diseases characterized by chronic inflammation including stroma formation in solid tumors, rheumatoid arthritis and inflammatory bowel disease, connective tissue diseases, atherosclerosis, heart failure, transplant rejection and wound healing to name a few. The progression of fibrosis in these diseases leads to the derangement of tissue architecture and subsequent failure of the organ. In many of these diseases current therapeutic approaches have only marginally contributed to cure and must be seen as approaches that delay the progression of the disease. However, in certain circumstances in the adult, diseased organs (for instance the kidney in glomeruloid nephritis, the liver after hepatitis, and the heart during ventricular hypertrophia) are capable of healing themselves with minimal damage to the tissue and its function. Tissue regeneration following damage to an organ during embryogenesis and infancy is also an example of tissue repair with minimal functional sequel. In the adult, a pregnant women together with the fetus is able to create a new functional organ, namely the placenta. Thus, the adult body has mechanisms by which to adequately repair damaged organs and even create new organs. Why the body does not always achieve this, and what causes progression in one instance, and healing in another, is largely unknown and is one of the main subjects of study in the lab. We have previously shown that one of the major players in the progression of diseases characterized by fibrosis is the microvascular pericyte.
AVAILABLE PROJECTS Isolation of stemcells that lead to cells with a fibrotic phenotype-defining the pericyte/fibroblast lineage The first line of investigation involves the
isolation and study of stem cells that define the pericyte-fibroblast lineage, and to identify different
stages of this differentiation process. Preliminary results show that five different stages are involved in this process. The project is to study differences in gene expression and proteins during this differentiation process using microarray techniques as well as proteonomics. Cell lineages have previously been defined for bone marrow hematopoietic cells, and has led to substantial breakthroughs in the treatment of a large array of hematological diseases. By defining this new cell lineage, novel insights into the process of fibrosis and potential modulation will be identified.
This project is basically the following: Isolation of these cells is already established. Cells will be analysed using FACS analysis to characterize their phenotype. Cells from each stage of differentiation will be isolated and processed for microarray analysis. This project I think would interest scientists whom are interested in stem cell biology, cell biology, phenotypical characterization and high throughput analysis. Gene therapeutic approach for studying fibrosis and blood vessel formation in the body The second line of investigation is to study cell progression and events that occur during blood vessel formation and fibrosis in the body. To this effect gene therapy techniques will be used inorder to introduce genes for growth factors into normal and diseased tissues, both individually and in combination. Effects of these growth factors will be studied using advanced morphological and physiological techniques which are being developed.