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Förslaget inkom 2003-12-04

Isolation of stemcells that lead to cells with a fibrotic phenotype-defining the pericyte/fibroblast lineage

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Introduction
The main focus of this group 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.

Several lines of investigation are currently being set up in the lab to address different aspects of the process of bloodvessel formation, fibrosis and tissue regeneration involving; gene therapy; microarray techniques combined with proteonomics; isolation of stem cells and how they are able to differentiate into collagen type I producing fibroblasts in the body and in the culture dish; low molecular weight drug therapy; and isolation of novel substances which may inhibit the development of fibrosis and tumor progression.

Project
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.


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