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Adipose Stem Cells: Molecular Basis of Pluripotency

Awarded: NOK 18.5 mill.

Stem cells reside in many adult tissues and are responsible for maintaining tissue homeostasis. Adipose tissue-derived mesenchymal stem cells (ASCs) display sufficient plasticity to differentiate into cell types outside their predicted developmental linea ge. This might create opportunities for autologous cell therapy. Nonetheless, virtually nothing is known on the molecular premise of stem cell-ness and only few studies have examined the effectiveness of ASCs in repairing damaged tissue. This proposal add resses whether human ASCs exist as distinct populations or as a continuum of cells at various stages of differentiation, whether epigenetic modifications, global and at specific promoters, can account for the genomic plasticity of ASCs, and investigates t he potential therapeutic potential of ASCs. We will characterize uncultured vs cultured ASCs at the levels of gene and protein expression, DNA methylation and epigenetic histone modifications at specific promoters. The second section explores the genomic plasticity of ASCs in terms of differentiation potential of monoclonal ASC cultures, and dedifferentiation to a pluripotent stage using a cell-free approach. The third section examines the therapeutic potential of ASCs by assessing their contribution to r epairing tissues such as cartilage, bone, vasculature and neurons. The PI (Prof. Philippe Collas) and co-PI (Dr. Jan E. Brinchmann) have acquired expertise in the handling of ASCs and in the techniques required to examine stem cell biology from the angles of genomic plasticity, epigenetics and medicine. The project regroups the complementary stem cell and nuclear reprogramming expertise of the PIs, incorporates novel technologies around cell culture and is supported by outstanding collaborators. The resu lts are expected to immensely enhance our understanding of the biology and therapeutic application potential of adult stem cells.

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