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Sarah Shelton, PhDPostdoctoral Research FellowMassachusetts Institute of Technology and Dana-Farber Cancer Institute
Microphysiological systems or “organ-on-chip” devices are three-dimensional models of simplified biological tissue that have greatly expanded the types of experiments and hypotheses that can be explored in vitro in recent years. My work focuses on vascularized models of the tumor microenvironment to understand the how the endothelial barrier interacts with circulating cells and stromal tissue in order to investigate factors that drive tumor growth, metastasis, and resistance to therapy. One illustration of these models is the observation of the metastatic process, which was accomplished by perfusing cells through vasculature-on-chip in the presence of plasma proteins to determine how the clotting cascade interacts with cancer cells and influences extravasation. Additionally, I have developed novel vascularized models of the tumor microenvironment using cells from surgical resections to generate patient-specific devices. The addition of primary cancer-associated fibroblasts altered several functional parameters, including vascular morphology, barrier function, angiogenesis, as well as immune cell recruitment, likely through cytokine signaling. One major challenge of performing in vitro immunotherapy studies arises from non-specific activation of T cells that occurs when mixing cells from different donors. Therefore, the combination of patient-specific cells and engineered vasculature will enable new immune-oncology studies with many possibilities, including basic science studies, precision medicine trials, and enabling rapid testing and translation of novel immunotherapies.
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