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Oral presentation

Stem cells possess multilineage capacity to be developed towards multiple stages of terminal cell differentiation. They represent the source for tissue growth and formation during development as well as the source for tissue regeneration throughout life. Embryonic stem cells can be developed into any cell of a whole organism, whereas adult tissue specific stem cells usually represent committed precursors, which display limited capacity to differentiate into terminally differentiated cells, e.g. cells of ektodermal, mesodermal or endodermal origin. There is however a vivid discussion about the plasticity of adult stem cells and recently a subset of bone marrow derived adult stem cells was shown to display a surprising capability for pluri- or multipotency. This discussion is ongoing and it comprises the debate about ethical problems of embryonic stem cell generation versus the versatility of adult stem cells which can be individually available without major problems. The definition of a stem cell is still not accurate in terms of marker molecules and within a population of adult stem cells there is probably a considerable variability as to their stage of commitment and differentiation. Thus an adequate method to describe a "stem cell" or precursor cell population may be to evaluate their differentiation capability after application of lineage specific stimuli. Stem cells can be used as tools and targets of new therapeutic strategies. In vitro stem cell propagation and subsequent autotransplantation is the basic way to replace stem cells for tissue regeneration. Such cell based strategies are already used in clinical medicine in conventional bone marrow and stem cell transplantation procedures using individual CD34+ stem cells for bone marrow replacement after marrow ablative therapy for haematological and other neoplasias. This form of therapy can theoretically be used for ex vivo propagation and autotransplantation procedures with or without genetic engineering. Experimental procedures use adult stem cells or crude marrow cells for injection into partially necrotic areas of tissues like in ischemic heart attacks. Other scenarios comprise in vitro expansion of stem cells followed by tissue engineering procedures using suitable scaffolds and recombinant growth and differentiation factors. Mesenchymal stem cells are already widely used in experimental therapy for in vitro production of bone, cartilage and ligaments. Thus tissue defects caused by malformations, accidental tissue destruction or infectious and degenerative diseases could be effectively cured. Aging is accompanied by a relative failure of tissue regeneration. Systemic approaches to target tissue specific stem cells using factors which induce waves of tissue regeneration represent one of several goals of the new section in medicine coined "Regenerative Medicine". Stem cell specific growth and differentiation factors and their respective signal transduction cascades, extracellular matrix and associated molecules and lineage specific transcription factors may be the molecular targets for drug development as well as systemic gene therapy. For mesenchymal stem cells factors influencing the osteogenic and chondrogenic pathway of differentiation are partially characterized. Recombinant factors injected into sites where mesenchymal stem cells can be recruited may produce ectopic tissue like the production of bone in muscle tissue after injection of bone morphogenetic proteins. These experiments basically show the prove of principle that tissue growth can be stimulated by addressing stem cells. To avoid the development of uncontrolled growth and subsequent functional problems and possibly tumour development many steps in tissue growth have to be controlled either by endogenous control mechanisms after patterning and contact inhibition or by controlling exogenous stimuli. The tools for the characterization of new genes, molecular modelling of signalling substances and high throughput systems to test small molecule ligands to modify cellular signals are nowadays available and should lead to stem cell targeted therapy exploiting small molecules and recombinant factors in the future.

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