Apoptosis is a genetic program that kills cells that proliferate too much or in the wrong place in the body. Transplanted stem cells hold great promise for the treatment of degenerative diseases. There are several reasons why understanding stem cell apoptosis will further the therapeutic use of stem cells. First, stem cells must be cultured in sufficient numbers for treatment. Second, to repair a tissue, a stem cell must survive and persist in the damaged tissue. Identifying ways to promote stem cell survival by blocking apoptosis will serve both these goals. Finally, there is a growing understanding that aberrant proliferation in stem cells can cause cancer. Specifically inducing apoptosis in transplanted stem cells would be a powerful strategy in limiting this cancer risk. The research proposed here investigates the role of key apoptotic genes in controlling stem cell behaviour. This work will serve as a strong and necessary foundation for achieving the longer term goal of facilitating stem cell therapy. Specifically, the proposed experiments investigate how stem cells regulate caspases, proteases that are key components of the apoptotic machinery. Preliminary data reveal that different viable mouse embryonic, adult rat mesenchymal and haematopoietic stem cells have higher caspase-like activity than viable non-stem cells. The long term goal is to determine the role of this activity in stem cell potency. The specific experiments described here will identify the protease responsible for the activity in mouse embryonic stem cells using a combination of biochemical and genetic approaches. There is controversy, both scientific and ethical over the therapeutic use of embryonic stem cells. Therefore, adult human mesenchymal stem cells will also be tested for the activ ity as this cell type has more therapeutic relevance.
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