title: MHC universal cells survive in an allogeneic environment after incompatible transplantation.
abstract: Cell, tissue, and organ transplants are commonly performed for the treatment of different diseases. However, major histocompatibility complex (MHC) diversity often prevents complete donor-recipient matching, resulting in graft rejection. This study evaluates in a preclinical model the capacity of MHC class I-silenced cells to engraft and grow upon allogeneic transplantation. Short hairpin RNA targeting β2-microglobulin (RN_shβ2m) was delivered into fibroblasts derived from LEW/Ztm (RT1(l)) (RT1-A(l)) rats using a lentiviral-based vector. MHC class I (RT1-A-) expressing and -silenced cells were injected subcutaneously in LEW rats (RT1(l)) and MHC-congenic LEW.1W rats (RT1(u)), respectively. Cell engraftment and the status of the immune response were monitored for eight weeks after transplantation. In contrast to RT1-A-expressing cells, RT1-A-silenced fibroblasts became engrafted and were still detectable eight weeks after allogeneic transplantation. Plasma levels of proinflammatory cytokines IL-1 α , IL-1 β , IL-6, TNF- α , and IFN- γ were significantly higher in animals transplanted with RT1-A-expressing cells than in those receiving RT1-A-silenced cells. Furthermore, alloantigen-specific T-cell proliferation rates derived from rats receiving RT1-A-expressing cells were higher than those in rats transplanted with RT1-A-silenced cells. These data suggest that silencing MHC class I expression might overcome the histocompatibility barrier, potentially opening up new avenues in the field of cell transplantation and regenerative medicine.
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany.
authors.forename: Constança
authors.initials: C
authors.lastname: Figueiredo
authors.affiliation: Institute for Laboratory Animal Science, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wedekind
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Vahlsing
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Nordrhein-Westfalen, Germany.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Horn
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany ; German Red Cross, Blood Services NSTOB, Institute Springe, Lower Saxony, 31832 Springe, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Seltsam
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Lower Saxony, 30625 Hannover, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D006649:Histocompatibility Antigens; C038353:histocompatibility antigens RT, rat