Self-renew and multilineage potential characterize stem cells. We have recently described that pancreas progenitor cells extracted from adult donors can be expanded long-term in vitro into 3D structures, which we have termed organoids. Pancreas organoids reproduce in vitro all the features of pancreas ductal epithelia, and have a limitless expansion potential. Thus, pancreas organoids promise to boost cell therapy of type 1 diabetes. We have recently observed that progenitor cells organoids preserve their genetic stability over a long time in culture. That represents an advantage, when compared to iPS or hES derived approaches, where genetic instability raises concerns for their future therapeutic applications. While progenitor organoids are promising for the future of cell therapy, bringing stem cell-based therapies to patients requires a reliable characterization (“knowing what the cells do and how they do it”, i.e. a phenotypic and molecular biology characterization), chemically well-defined culture media, and the capacity of mass-production under GLP/GMP conditions. The LSFM4LIFE consortium aims to the mass production of pancreas organoids for the cellular therapy of type 1 diabetes. The goals of the project are: (1) optimize growth and differentiation of human pancreas stem-cell organoids by employing phenotypic and molecular high-throughput screening (2) standardize the growth and differentiation of the organoids under well-defined biochemical conditions, and (3) achieve GLP/GMP-production of the human organoids for preclinical studies and phase I clinical studies. The close collaboration in the consortium between academic researchers and industry, as well as its cross-disciplinary composition, are essential to realize the goals of the project. The work packages of the project will have a technological impact in the form of patents and first market replication.

Revision endoprosthesis are mostly associated with post-surgical physical symptoms that can lead to long-term confinement to bed and in severe cases to implant rejection. Severe inflammatory reactions in the endoprosthesis shaft can occur due to a previous long-term prosthesis. Medically managing the inflammation process is challenging as it is difficult to introduce drugs to the site of inflammation after implantation of the revision endoprosthesis. EVPRO overcomes this problem by using human mesenchymal stem cell derived extracellular vesicles (MSC-EVs) which are known to suppress inflammatory reaction in humans, exert pro-regenerative effects in osteogenic setting and successfully treat patients with steroid-refractory graft-versus-host disease. In this project the MSC-EVs will be applied in direct physical proximity to the site of inflammation and will therefore affix on the implant surface to deliver their anti-inflammatory and regenerative effect in response to the local inflammation status. This will be achieved by safe integration of the MSC-EVs in a smart biodegradable hydrogel that is absorbed into the micropores of a TiO2 coating on the surface of conventional titan endoprosthesis. EVPRO enables the progression of each individual technology, along with EVPRO system level integration developments, into pre-clinical trials, this means in detail, the development of a GMP conformed large scale production of MSC-EVs, the establishing of an uniform method to purify and select the most potential MSC-EVs with a microfluidic system and the design of a self-regulated hydrogel as protection matrix of MSC-EVs with the function to store and release MSC-EVs in response to the inflammation status, The EVPRO project is an integration of multidisciplinary post-proof of concept technologies which enables the successful resolution of the enhanced osseointegration of endoprosthesis for osteoarticular tissue regeneration.