The LSFM4LIFE consortium realized the major goals envisioned and planned in the project.
Objective 1: the groups at the University of Cambridge have shown that hPOs can be expanded long-term, from both fresh and cryopreserved human pancreas tissue in a chemically defined, serum-free medium with no detectable tumorigenicity.
hPOs can be clonally expanded, genetically manipulated and are amenable to culture in a chemically defined hydrogel. Therefore, the LSFM4LIFE consortium has successfully established hPOs as an abundant source of pancreas ductal cells that retain the characteristics of the original tissue. These results have been published in BMC Developmental Biology (
https://doi.org/10.17863/CAM.48839(si apre in una nuova finestra)).
Objective 2: Goethe University Frankfurt realized the hardware, workflow and the corresponding protocols for performing high-throughput analysis of hPOs with Light Sheet Fluorescence Microscopy (LSFM). The results of this work have been recently published in Nature Scientific Reports (
https://doi.org/10.1038/s41598-019-53380-2(si apre in una nuova finestra)). Moreover, a monolithic version of the high-throughput LSFM (mHT-LSFM) has been realized. The mHT-LSFM incorporates the operating principles of the HT-LSFM prototype in a compact and user-friendly device that can be operated by non-specialists in microscopy, thus greatly expanding the possibility of adoption of light-sheet microscopy technology by other laboratories working with organoids and further types of 3D cultures for regenerative medicine and cell-based therapy.
Objective 3: a primary goal of LSFM4LIFE, which has been achieved by Cellendes. A novel dextran-based hydrogel efficiently supporting the growth of hPO has been synthesized and tested. The new hydrogel, fully defined and GMP compliant, allows the expansion of hPO from frozen stocks as well as from tissue biopsies. These results have been published in BMC Developmental Biology (
https://doi.org/10.17863/CAM.48839(si apre in una nuova finestra)).
Objective 4: Cell Factory at Policlinico Hospital in Milan has accomplished a further major goal of LSFM4LIFE, namely developing the GMP workflow for the clinical-grade manufacture of hPO. These results have been published in the journal Stem Cell Research & Therapy (“Standardized GMP-compliant scalable production of human pancreas organoids”, doi: 10.1186/s13287-020-1585-2) and featured in the editorial
https://doi.org/10.1186/s13287-020-1586-1(si apre in una nuova finestra)).
Lonza Netherlands has accomplished all the planned tasks, elaborating in total four comprehensive dossiers, which outline a full roadmap leading to the commercial production of hPO and their use as a cellular medicinal product.
During P3, ProSciencia joined the consortium for the dissemination activities. ProSciencia has further outstandingly carried on the dissemination work of LSFM4LIFE, by ensuring a day-by-day updating of the LSFM4LIFE website (www.lsfm4life.eu) as well as daily coverage of the advancements in the research and therapy of Diabetes Type 1 on Twitter, presenting both the results of the consortium and the ones of other researchers external to LSFM4LIFE. In addition, 5 new videos describing the work of LSFM4LIFE and including interviews with the scientists working on the project have been produced in P3 (
https://lsfm4life.eu/2019/new-project-videos/(si apre in una nuova finestra)). Finally, during P3 the LSFM4LIFE consortium has organized and supported two international conferences: the European Organoids Symposium - EOS2019 (www.eos2019.eu) and the Light Sheet Microscopy Conference - LSFM2019 (www.lsfm2019.eu).
