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In 2002, the mechanisms of immune escape from tumors were still not elucidated, leading to the paradox of the coexistence of T-cell-mediated anti-tumor immunity and unexplained metastatic development in T-cell areas of lymphoid organs. We have notably demonstrated that tumor-infiltrating dendritic cells are naturally loaded with tumor-associated antigens (Preynat-Seauve et al., 2006) and capable of protecting against tumor development. In an effort to understand the paradox of metastatic development in T-cell areas of lymphoid tissues, our main achievement in this field was to understand for the first time that tumor-associated antigens were tolerated by antigen-presenting cells in draining lymph nodes distant from the tumor site, thus allowing metastatic development in lymphoid tissues (Preynat-Seauve et al., 2007).
The increasing emergence of cell therapy applications from embryonic Pluripotent Stem Cells (ePSCs) in 2006 allowed us to work on several tissue engineering applications. We described the first possibility to create a 3D self-organized neural tissue from ePSCs (Preynat-Seauve, Suter, et al., 2009), thus opening the way to the important concept of human neural tissue engineering. We also developed the possibility of modelling glioblastoma in ePSC-derived neural tissue (Nayernia et al., 2013). Regarding the cell therapy potential of ePSC-derived cells, we have also demonstrated the immunogenicity of ePSC-derived neural grafts under allogeneic conditions (Preynat-Seauve, de Rham, et al., 2009)
More recently, we have conducted research on the impact of environmental regulations of Adipose-derived Stromal Cells (ASCs). We demonstrated that ASC spheroids improved fat graft uptake for reconstructive surgery applications compared to ASC suspensions (El Harane et al., 2022). To maintain the benefits of ASC clustering while adding pro-angiogenic regulations, we investigated gelatin-based scaffolds, reasoning that the RGD of gelatin might enhance the angiogenic capabilities of ASCs. We found that gelatin promoted a strong angiogenic response on wounds (N.C. Brembilla et al., 2023). The combination of ASCs with gelatin-based scaffolds has also been patented (Cellular substitute and methods of preparation thereof, WO2021053132A1) and has been the subject of a preclinical study. This new ASC regulation has the potential to develop a new stage of ASC regulation, promising for the treatment of chronic wounds, as discussed in our recently published invited review on this topic (N. C. Brembilla et al., 2023). A spin off from the University of Geneva, Heketiss SA, has been established to ensure the pharmaceutical development of angiogenic ASCs.
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EXPERIMENTAL DERMATOLOGYno. 3 (2024)
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Cellsno. 1001 (2023): 1001-1001
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