title: Local Inhibition of Complement Improves Mesenchymal Stem Cell Viability and Function After Administration.
abstract: The results of recent clinical trials using mesenchymal stem cells (MSCs) have been unsatisfactory, indicating that current MSC-based therapies need to be improved. We and others have previously demonstrated that MSCs activate complement by unknown mechanisms after infusion, leading to damaged MSCs. In the study reported here, we found that incorporation of N-glycolylneuraminic acid onto MSCs during in vitro culture was a factor in the activation of complement by MSCs. In addition, we developed a way to "paint" heparin onto MSCs. This novel method improved the viability of MSCs and enhanced their function after infusion by directly inhibiting complement and by recruiting factor H, another potent complement inhibitor in serum, onto the surface of the MSCs. These data suggest that cell-surface engineering of MSCs with heparin to locally inhibit complement activation on MSCs might be a straightforward and effective method for improving the outcome of current MSC-based therapies.
authors.affiliation: Department of Immunology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: John
authors.initials: J
authors.lastname: Fung
authors.affiliation: Department of Immunology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003167:Complement Activation; D017242:Complement Factor H / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007165:Immunosuppression Therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009438:Neuraminic Acids / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D009438:Neuraminic Acids; C032592:N-glycolylneuraminic acid; D017242:Complement Factor H; D006493:Heparin; D003165:Complement System Proteins