title: Immune effects of mesenchymal stromal cells in experimental stroke.
abstract: Preclinical trials confirmed the potential of mesenchymal stromal cells (MSCs) to improve functional recovery after experimental stroke. Beneficial effects of MSCs are often attributed to their immunosuppressive/immunomodulatory functions. Surprisingly, the influence of MSCs on the immune system after stroke is poorly understood, but requires special consideration because cerebral ischemia is associated with stroke-induced immunodepression that predisposes to bacterial infections with increased mortality. In this study, we intravenously transplanted syngeneic murine bone marrow-derived MSCs (mMSCs) into C57BL/6 mice at 6 hours after transient middle cerebral artery occlusion (MCAo; 60 minutes) to investigate the impact of MSCs on stroke-induced immunodepression. Transplantation of syngeneic splenocytes or phosphate-buffered saline (PBS) served as controls. An immune status was determined by flow cytometry on days 3 and 14 after MCAo, which did not reveal any negative effects of cell transplantation on stroke-induced immunodepression. Although our mMSCs were found to exert immunosuppressive effects in vitro, stroke-mediated immune cell dysfunction was not altered by mMSCs in ex-vivo stimulation assays with lipopolysaccharide or concanavalin A. Moreover, systemic inflammatory cytokine levels (interleukin-6, tumor necrosis factorα, interferonγ, monocyte chemoattractant protein-1) remained unchanged in the sera of mice after cerebral ischemia and cell transplantation. These results reduce safety concerns about MSC administration in ongoing clinical stroke trials.
authors.affiliation: Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Scheibe
authors.forename: Juliane
authors.initials: J
authors.lastname: Ladhoff
authors.forename: Jojanneke
authors.initials: J
authors.lastname: Huck
authors.forename: Maik
authors.initials: M
authors.lastname: Grohmann
authors.forename: Katja
authors.initials: K
authors.lastname: Blazej
authors.forename: Arif
authors.initials: A
authors.lastname: Oersal
authors.forename: Nevena
authors.initials: N
authors.lastname: Baeva
authors.forename: Martina
authors.initials: M
authors.lastname: Seifert
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007108:Immune Tolerance; D007275:Injections, Intravenous; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D020521:Stroke / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D014181:Transplantation Immunology
chemical_list: D016207:Cytokines