title: Induction of macrophage-like immunosuppressive cells from mouse ES cells that contribute to prolong allogeneic graft survival.
abstract: Recent progress in regenerative medicine has enabled the utilization of pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) as a donor resource for transplantation. However, immune suppression is still needed when the donor-recipient combination is allogeneic. Protection of ESCs-derived grafts from host immune response might be achieved thought the utilization of immunosuppressive cells generated from ESCs. In the present study, we show that a certain fraction of immunosuppressive cells can be generated from ESCs and help to suppress immune response against allogeneic grafts. ESCs-derived suppressor cells (ES-SCs) resembled macrophages in terms of cell surface molecule and gene expressions. Furthermore, gene expression analysis including microarray showed that ES-SCs have M1/M2 hybrid phenotype with high expression of genes correlated to immunosuppression of T cell response. Indeed, ES-SCs were effective to block allogeneic T cell proliferation in a nitric oxide-dependent manner, and prolonged the survival of ESCs-derived embryoid bodies or cardiomyocytes grafts transplanted into mouse kidney capsule. Thus, we consider the potential use of these ESCs-derived macrophage-like immunosuppressive cells as cellular therapies to promote long-term graft survival in future therapies.
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan; Department of Urology St. Marianna University School of Medicine, Miyamae-ku, Kawasaki City, Kanagawa, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kudo
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Wada
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hyuma
authors.initials: H
authors.lastname: Tsuji
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Otsuka
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Baghdadi
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kojo
authors.affiliation: Department of Urology St. Marianna University School of Medicine, Miyamae-ku, Kawasaki City, Kanagawa, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Chikaraishi
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Seino
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D007165:Immunosuppression Therapy; D007519:Isoantigens / Q000276:immunology; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008809:Mice, Inbred C3H; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation*; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology; D014184:Transplantation, Homologous
chemical_list: D007519:Isoantigens