title: Gamma irradiation preserves immunosuppressive potential and inhibits clonogenic capacity of human bone marrow-derived mesenchymal stromal cells.
abstract: Mesenchymal stromal cells (MSCs) are promising candidates for the treatment of graft-versus-host and autoimmune diseases. Here, by virtue of their immunosuppressive effects, they are discussed to exhibit inhibitory actions on various immune effector cells, including T lymphocytes that promote the underlying pathology. While it becomes apparent that MSCs exhibit their therapeutic effect in a transient manner, they are usually transplanted from third party donors into heavily immunocompromised patients. However, little is known about potential late complications of persisting third party MSCs in these patients. We therefore analysed the effect of gamma irradiation on the potency and proliferation of MSCs to elucidate an irradiation dose, which would allow inhibition of MSC proliferation while at the same time preserving their immunosuppressive function. Bone marrow-derived MSCs (BM-MSCs) were gamma-irradiated at increasing doses of 5, 10 and 30 Gy and subsequently assessed by colony formation unit (CFU)-assay, Annexin V-staining and in a mixed lymphocyte reaction, to assess colony growth, apoptosis and the immunosuppressive capacity, respectively. Complete loss of proliferative capacity measured by colony formation was observed after irradiation with a dose equal to or greater than 10 Gy. No significant decrease of viable cells was detected, as compared to non-irradiated BM-MSCs. Notably, irradiated BM-MSCs remained highly immunosuppressive in vitro for at least 5 days after irradiation. Gamma irradiation does not impair the immunosuppressive capacity of BM-MSCs in vitro and thus might increase the safety of MSC-based cell products in clinical applications.
authors.affiliation: Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Dresden, Germany.
authors.forename: Ana Valéria Gouveia
authors.initials: AV
authors.lastname: de Andrade
authors.forename: Julia
authors.initials: J
authors.lastname: Riewaldt
authors.forename: Rebekka
authors.initials: R
authors.lastname: Wehner
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.forename: Marcus
authors.initials: M
authors.lastname: Odendahl
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Torsten
authors.initials: T
authors.lastname: Tonn
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology* / Q000528:radiation effects; D001327:Autoimmune Diseases / Q000276:immunology; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology* / Q000528:radiation effects; D002454:Cell Differentiation / Q000276:immunology* / Q000528:radiation effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D008875:Middle Aged; D013601:T-Lymphocytes; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents
keywords: GvHD; gamma irradiation; immunosuppression; mesenchymal stromal cells