CellCAN: A Unique Enabler of Regenerative Medicine and Cell Therapy in Canada

Regenerative Medicine and Cell Therapy (RMCT) is paving the way for the most innovative and promising medical breakthroughs of the 21st century. Indeed, its curative potential is immense and builds on the already proven benefits of stem cell transplantation. Successful and broad clinical implementation of RMCT, as well as reaping of its full social and economic benefits, is contingent on the resolution of a range of issues. The CellCAN network, a not-for-profit corporation, was created to tackle these challenges, gathering the key forces of the numerous Canadian organizations involved in basic research, assay development, manufacturing, clinical research, clinical trials, legal and ethical regulations, and policies, all working to move RMCT forward. CellCAN creates a national enterprise by bringing together a community of renowned researchers, industries, clinicians, funders and regulators, and aligning it with cell-handling facilities involved in processing cell products and other products for cell therapy clinical trials to ensure capacity and know-how for stem cell research and efficient execution of cell therapy clinical trials. CellCAN is uniquely positioned to accelerate the implementation of RMCT in Canada and disseminate novel developments and findings, thus significantly contributing to the world’s knowledge in cellular therapeutics. As such, the CellCAN model could also serve as a useful benchmark to accelerate RMCT implementation in other countries

Superoxide Dismutases in Candida albicans: Transcriptional Regulation and Functional Characterization of the Hyphal-induced SOD5 Gene

Superoxide dismutases (SOD) convert superoxide radicals into less damaging hydrogen peroxide. The opportunistic human pathogen Candida albicans is known to express CuZnSOD (SOD1) and MnSOD (SOD3) in the cytosol and MnSOD (SOD2) in the mitochondria. We identified three additional CuZn-containing superoxide dismutases, SOD4, SOD5, and SOD6, within the sequence of the C. albicans genome. The transcription of SOD5 was up-regulated during the yeast to hyphal transition of C. albicans, and SOD5 was induced when C. albicans cells were challenged with osmotic or with oxidative stresses. SOD5 transcription was also increased when cells were grown on nonfermentable substrates as the only carbon source. The Rim101p transcription factor was required for all inductions observed, whereas the Efg1p transcription factor was specifically needed for serum-modulated expression. Deletion of SOD5 produced a viable mutant strain that showed sensitivity to hydrogen peroxide when cells were grown in nutrient-limited conditions. Sod5p was found to be necessary for the virulence of C. albicans in a mouse model of infection. However, the sod5 mutant strain showed the same resistance to macrophage attack as its parental strain, suggesting that the loss of virulence in not due to an increased sensitivity to macrophage attack

Immune-Deficient Drosophila melanogaster: A Model for the Innate Immune Response to Human Fungal Pathogens

We explored the host-pathogen interactions of the human opportunistic fungus Candida albicans using Drosophila melanogaster. We established that a Drosophila strain devoid of functional Toll receptor is highly susceptible to the human pathogen C. albicans. Using this sensitive strain, we have been able to show that a set of specific C. albicans mutants of different virulence in mammalian infection models are also impaired in virulence in Drosophila and remarkably display the same rank order of virulence. This immunodeficient insect model also revealed virulence properties undetected in an immunocompetent murine model of infection. The genetic systems available in both host and pathogen will enable the identification of host-specific components and C. albicans genes involved in the host-fungal interplay