Mesenchymal Stromal Cells (MSCs) represent an attractive treatment for patients with steroid refractory acute Graft versus Host Disease (GvHD) after allogeneic Haematopoietic Stem Cells Transplantation (HSCT). However, responses to MSCs are rather unpredictable and this is largely the consequence of a heterogeneous cell preparation, and a significant part of the patients do not respond to the treatment.
It has recently been discovered that the therapeutic activity of MSCs depends on their ability to undergo in vivo apoptosis and consequently to reprogram inflammation via re-educating monocytes/macrophages towards an immunosuppressive phenotype. This discovery provides a new mechanistic angle to classify MSCs based on their therapeutic potential. The aim of this project is to provide evidence that MSCs can be classified based on their sensitivity to undergo apoptosis and to drive the differentiation of tolerogenic macrophages. The results will have an invaluable impact on the manufacturing protocols of MSCs, since we will be able to classify any MSC preparation and identify MSCs with the most potent therapeutic profiles by selecting the best donor and cell source. This ultimately will translate into a better management of GvHD, with the possibility to extend the indication of curative allogeneic HSCT to most patients with leukaemia.
Based on the fruitful collaborations over the past years between the Regenerative and Haematological Medicine group led by Prof. Francesco Dazzi at King’s College London and the Department of Internal Medicine I led by Prof. Martin Bornhäuser at University Hospital Carl Gustav Carus, this collaboration has not only stemmed in co-authorships in peer-reviewed published papers, but also been awarded with several awards (Jon J. van Rood Award, European Society of Blood and Marrow Transplantation – 2018, Best Presentation Award, Bloodwise – 2018). This project will represent the natural development of these achievements.