title: Painting factor H onto mesenchymal stem cells protects the cells from complement- and neutrophil-mediated damage.
abstract: Mesenchymal stem cells (MSCs) are undergoing intensive testing in clinical trials as a promising new therapy for many inflammatory diseases and for regenerative medicine, but further optimization of current MSC-based therapies is required. In this study, we found that in addition to direct complement-mediated attack through the assembly of membrane attack complexes (MACs) that we and others have recently reported, of the released complement activation products, C5a, but not C3a, activates neutrophils in the blood to further damage MSCs through oxidative burst. In addition, we have developed a simple method for painting factor H, a native complement inhibitor, onto MSCs to locally inhibit complement activation on MSCs. MSCs painted with factor H are protected from both MAC- and neutrophil-mediated attack and are significantly more effective in inhibiting antigen-specific T cell responses than the mock-painted MSCs both in vitro and in vivo.
authors.affiliation: College of Life Sciences and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China; Department of Immunology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Immunology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: John
authors.initials: J
authors.lastname: Fung
authors.affiliation: College of Life Sciences and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China; Department of Immunology, Cleveland Clinic, Cleveland, OH, USA. Electronic address: linf2@ccf.org.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003167:Complement Activation / Q000187:drug effects*; D017242:Complement Factor H / Q000276:immunology / Q000494:pharmacology*; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D044087:Receptor, Anaphylatoxin C5a / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D044087:Receptor, Anaphylatoxin C5a; D017242:Complement Factor H; D003165:Complement System Proteins
keywords: Complement; Factor H; MSC; Neutrophil; Therapy