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Cytomatrix |
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An Artificial Thymus for the Production of T Cells | ||
| National Institute of Standards and Technology/ATP The purpose of this ATP proposal is to develop an artificial thymus as a production bioreactor to manufacture T cells ex vivo for cellular immunotherapy. The artificial thymus is based on the ability to mimic the microenvironment of the thymus (the organ where T cells develop) using a biocompatible, porous, three dimensional (3-D) cell growth matrix termed Cellfoam (U.S. patent 5,282,861). The matrix is pre-established with thymic stromal cells and used as an organotypic culture device to produce T cells from normal human hematopoietic stem cells (HSCs) in the absence of exogenous factors, including cytokines and serum. The artificial thymus will be developed through the testing and optimization of the Cellfoam prototype using two parallel approaches: a human thymic-human HSC allogeneic system and a murine thymic-human HSC xenogeneic model system. Aim 1: Optimization of thymic-HSC culture in Cellfoam; analysis of derived T cells Aim 2: Scale-up of the ex vivo T cell production bioreactor; analysis of antigen responsiveness Aim 3: In vivo testing of antigen-reactive T cells |
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