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IntraEuropean Marie-Curie Fellowship "StemForStroke"

Marie CurieStem cell research offers a revolutionized perspective of regenerative medicine for severe medical conditions including ischemic stroke. Introducing stem cell research to ISD, Dr. Athanasios Lourbopoulos holds an IntraEuropean Marie-Curie Fellowship to study the graft-host interactions and in vivo secretome of mesenchymal stem cells in experimental stroke (Project Number PIEF-GA-2013-625970, "StemForStroke"). Under the specific project, Dr. Lourbopoulos is working in the Laboratory of Experimental Stroke Research (ISD, LMU Munich) under the supervision of Prof. Nikolaus Plesnila.

Within the framework of his Fellowship Dr. Lourbopoulos studies the bone marrow stromal cells (BMSCs), a subtype of mesenchymal stem cells, in experimental ischemic stroke.

Despite the reported benefits of these cells for neurodegenerative disorders (via mechanisms such as trophic support, tissue revascularization and immunomodulation) the exact in vivo repertoire of their secreted molecules (secretome) is not known so far. They only available data come from in vitro studies that show BMSCs capable of secreting trophic factors, micro RNAs and vesicles.

Within the frame of the present Marie-Curie Fellowship Dr. Lourbopoulos studies for the first time the in vivo secretome of BMSCs after their transplantation in animals with ischemic stroke. We chose to transplant the BMSCs into the cerebrospinal fluid (CSF) compartment because it has the advantage of close vicinity to the ischemic region and is clear enough to allow for Proteomics analysis (with Liquid Chromatography Mass Spectrometry, LC/MS). The main hypothesis is that BSMCs will exert neuroprotective effects to the peri-infarct regions via secreted molecules (paracrine route) or via modulation of local host reactions. If our hypothesis proves correct, it could provide the basis for a "cell-free" stem cell treatment for ischemic stroke, via utilization and understanding of the BMSCs secretome.

Up to date, for the needs of the specific project, Dr. Lourbopoulos had to establish new techniques in our Institute. As a prerequisite for proper, translational, preclinical testing of the BMSCs, he has developed the concept of "mouse post-stroke care", which removes the mortality bias from the experimental stroke model of filament MCAo and resolves a long-lasting and highly debated problem of the field (Figure 1a). Following that, he has established and worked with mouse and human (collaboration with a company) primary BMSCs cell lines (Figure 1b). In addition, he has optimized a protocol of CSF collection from mice for highly efficient and ultraclean CSF collection, in order to achieve high quality of CSF for analysis with Liquid Chromatography Mass Spectrometry (collaboration with AG Prof. S. Lichtenthaler) (Figure 1c). Evidently, he uses these tools to study the secretome, behavior and BMSCs-host interactions after their transplantation into the CSF compartment (Figure 1d), in animals with severe stroke.

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Figure 1. Tools developed under the "StemForStroke" project (a-c) and their application (d) for the in vivo study of BMSCs CSF secretome after stroke.

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