Third-party funded: SEVRIT

Production and quality control of stem cell-derived extracellular vesicles for novel regenerative and immunomodulating therapy approaches

Funded by the state of North Rhine-Westphalia via financial resources from the European Regional Development Fund (ERDF) 2014-2020 ,, Investment for Growth and Jobs", project no. EFRE-0800395

Stem cell therapies, especially with mesenchymal stem cells (MSC), are a promising option for the medical treatment of different degenerative and immunological diseases. Their use in therapies for stroke, cardiac infarction or chronic inflammatory processes such as Morbus Crohn or multiple sclerosis has been investigated for years, and several studies on the topic yielded promising results. However, stem cell transplantation also bear risks: It can cause severe rejection reactions such as Graft-versus-host Disease (GvHD) or lead to uncontrolled proliferation of stem cells and tumour development.

At the same time, recent studies have shown that the beneficial effects are not mediated by the whole cells but rather by so called extracellular vesicles (EV) that are secreted from the MSCs. The SEVRIT project is based on this idea: Instead of “classical” stem cell therapies, the project partners focus on a vesicle-based approach that offers all the advantages of stem cell transplantation, but considerably reduces the effort and side effects of the therapy, as MSC-EVs have no tumorigenic potential and can be sterile-filtered. Thus they are easier to handle in therapy. Recent results are promising: The project partners were able to show in mice that neurons recover comparably well after a stroke if they are treated either with whole MSCs or with MSC-derived vesicles. In further animal experiments simulating a lack of oxygen (anoxia) during birth, they reached a much lower epilepsy burden than in control experiments. Furthermore, the partners successfully treated a patient who developed a severe GvHD after bone marrow transplantation. Thus this novel therapy approach is a versatile tool and might be able to provide all advantages of somatic stem cell transplantation without causing side effects.

In the scope of SEVRIT the project partners aim to establish production and processing of MSC-EVs under GMP (Good Manufacturing Practice) conditions and to standardise quality control. Furthermore, MSC cell lines will be generated that should enable large-scale production of EVs in the medium term, and cell culture conditions will be optimised to further increase production rates. The long-term aim of this work is to apply for a manufacturing authorisation for an individualised and GMP-compliant production of MSC-EVs and to establish the method systematically on a large scale. It will then be used as treatment for different diseases such as stroke, cardiac infarction, anoxia or GvHD.

The SEVRIT project partners, besides ISAS, are several institutions of the University of Duisburg-Essen (Faculty of Medicine of the UDE; Institute for Transfusion Medicine, Clinic for Bone Marrow Transplantation, Clinic for Ear, Nose, and Throat Medicine, and Institute for Medical Microbiology of the University Clinic Essen) as well as the Particle Metrix GmbH and the PL BioScience GmbH.