As a result of growing evidence of their therapeutic potential in cancer, infectious diseases, and tissue repair, there is an enormous increase in the research and discovery of cell-based medical treatments that require cultured cells. A large unmet need exists for a cost-effective system that will facilitate the development of clinical cell production capability with high outcome reliability and compliance to increasingly strict regulatory guidelines. The proposed system would provide a sterilely closed cell culture design with general flexibility to enable researchers to develop and optimize a wide range of production processes, over a variety of cell types, that can directly progress to routine clinical use. The system would incorporate Aastrom's single-pass perfusion technology already established as a highly effective and reliable method for primary human cell production, implemented in a culture chamber supported by a sterile closed fluid path. This innovative system would provide operational steps that can be performed when and as required by the user (e.g. medium priming, cell inoculation, non-adherent cell removal, antigen loading, gene transduction, re-inoculation, cell harvest) using a robotic cell processor instrument that minimizes user variability and biological performance of the system will be tested. An adherent cell process (stoma/mesynchemal stem cells) and a suspension cell process (antigen-pulsed T-cells) will be evaluated for cell yield, viability, flow cytometric phenotype, and function as compared to a representative research method (e.g. well plates, flasks) to establish performance of the system. In Phase II, enhancements will be implemented, broadened characterization testing will be performed, methods will be implemented for cost-effective manufacture of the system, and a collaboration will be identified and initiated for external use of the system to develop a unique cell process of mutual interest. The overall goal of the proposed work is to provide the research community with an effective solution for the development of GMP compliant therapeutic cell production and a pathway to bring the cells into clinical use. The overall goal of the proposed work is to develop a system that would provide a sterilely closed cell culture design with general flexibility to enable researchers to develop and optimize a wide range of production processes, using a variety of cell types, that can directly progress to production for routine clinical use. This system would be comprised of a single-use disposable cell growth cassette and robotic cell processor instrument with software providing user selected automated sequences, which can be performed as desired. Specific Phase I aims include: 1. Define specifications for the system. 2. Design and construct a prototype of the system (cell growth cassette and robotic cell processor). and 3. Test the prototype system using two significantly different cell culture processes that have good clinical potential.
