The last summer meeting of the LSFM4LIFE project was organized at the Representation of the State of Hesse in Brussels on 28th June 2019. It was an excellent opportunity for all the partners to meet again, exchange ideas and views, learn about the progress made in other work packages and plan for the final six months of the project.
After a welcome by Jan Schonebeck of the Representation of the State of Hesse, each partner had half an hour to summarize the work of the past months and to present the current status. In the absence of Meritxell Huch, it was Nicole Prior (also from the Gurdon Institute) who started the meeting by reporting on the Huch lab’s work on the expansion, characterisation and long-term safety of adult human pancreatic organoids (hPOs). This was an excellent introduction into the subject, as she started with the basic questions that drove the work: Can we generate hPOs and can these provide a possible T1D cellular therapy? She explained how hPOs can be readily generated, expanded and cryopreserved, and described their morphology and marker expression. She also discussed how the hydrogel defined by Cellendes affected the expansion rate. Finally, she presented different strategies for differentiating hPOs.
The next speaker was Nikitas Georgakopoulos of Kourosh Saeb-Parsy’s lab at Cambridge University, who started by reminding everybody of the aims of his task: evaluate the safety of hPOs in vitro and in vivo as a potential clinical therapy. This was done by studying the genetic stability of hPO cultures over time and assessing the in vivo safety of hPOs after transplantation into mice.
Work package 4 “Optimization and Quality Control” was presented by Lotta Hof and Till Moreth of Francesco Pampaloni’s team in Frankfurt. The presentation covered work with murine and human POs in Cellendes’ new hydrogel, immunofluorescent analyses of hPOs initiated by the project partner in Milan, liquid culture experiments in different environments, studies of hPO spheroid formation, cultivation of organoids in FEP-foil cuvettes as well as live imaging and high-throughput microscopy.
The next talk by Wolfgang Moritz (InSphero) was also on work package 4. He described the recent activities in his group, including the functional assessment of beta-cell function, scaling up the experiments to a 348-well plate and “painting” cells by adeno-associated virus (AAV) transduction, and concluded with a summary of the pancreatic islet discovery platform development.
The lunch break was not really a break from work for everybody, as Conny Heinzen and Lisa Schisanowski from RiedbergTV had travelled to Brussels to film the participants of the meeting and make some interviews. This video material will be used to make several clips about LSFM4LIFE in order to present the project to a broader public.
After lunch, Brigitte Angres (Cellendes) talked about her team’s efforts to produce a chemically defined hydrogel for hPO culture within the work package “Biomimetic Hydrogel Scaffold”. She described the disadvantages of PVA gels regarding the isolation of hPOs for further processing, which led her to think about using dextran-based gels. She then went on detailing the successful experiments with this system and its biomimetic modifications, emphasizing that in total 16 hydrogel compositions have been developed for investigation of hPO growth and the maintenance of the progenitor status.
Work package 6, the translation to GMP, was covered by two presentations. The first came from Lorenza Lazzari (Fondazione IRCCS Ca’ Granda Policlinico, Milan), the other from Bart van Dijk, who recently took over the management of the project at Lonza Netherlands. Lorenza described the hPO isolation protocols developed in her lab, starting from pancreas raw material. She explained the feasibility of GMP-compliant automated generation of undifferentiated hPOs that are suitable for biobanking and described the characterization of the growth properties, gene expression and immunophenotypic profile. She stressed that they implemented as much as possible GMP-compliant isolation/expansion and freezing protocols.
Bart presented Lonza’s work to develop a strategy for the translation of the hPO production to a GMP-compliant process focusing on sustainable late clinical and commercial phases. He started by detailing the gaps to be addressed and giving an updated market analysis, and thereafter focused on an exhaustive scale up and cost analysis of the current process.
The communication and dissemination work package was covered by Steffen Lindek (ProSciencia), who presented a summary of what he had been doing in the first three months since joining LSFM4LIFE in April. This was also the opportunity for the partners to discuss the next big event in terms of dissemination: EOS2019, the European Organoids Symposium, that will be organized in Milan in September.
The last presentation of the day was made by Manuela Martorana, who is responsible for the management of EC-funded projects at the Fondazione IRCCS Ca’ Granda Policlinico, Milan. She presented the current budgetary situation and answered many questions relating to the way expenses would be reviewed by the EC at the end of the project.