title: Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells.
abstract: The advantages of using induced pluripotent stem cells (iPSCs) instead of embryonic stem (ES) cells in regenerative medicine centre around circumventing concerns about the ethics of using ES cells and the likelihood of immune rejection of ES-cell-derived tissues. However, partial reprogramming and genetic instabilities in iPSCs could elicit immune responses in transplant recipients even when iPSC-derived differentiated cells are transplanted. iPSCs are first differentiated into specific types of cells in vitro for subsequent transplantation. Although model transplantation experiments have been conducted using various iPSC-derived differentiated tissues and immune rejections have not been observed, careful investigation of the immunogenicity of iPSC-derived tissue is becoming increasingly critical, especially as this has not been the focus of most studies done so far. A recent study reported immunogenicity of iPSC- but not ES-cell-derived teratomas and implicated several causative genes. Nevertheless, some controversy has arisen regarding these findings. Here we examine the immunogenicity of differentiated skin and bone marrow tissues derived from mouse iPSCs. To ensure optimal comparison of iPSCs and ES cells, we established ten integration-free iPSC and seven ES-cell lines using an inbred mouse strain, C57BL/6. We observed no differences in the rate of success of transplantation when skin and bone marrow cells derived from iPSCs were compared with ES-cell-derived tissues. Moreover, we observed limited or no immune responses, including T-cell infiltration, for tissues derived from either iPSCs or ES cells, and no increase in the expression of the immunogenicity-causing Zg16 and Hormad1 genes in regressing skin and teratoma tissues. Our findings suggest limited immunogenicity of transplanted cells differentiated from iPSCs and ES cells.
authors.affiliation: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Araki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Uda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hoki
authors.forename: Misato
authors.initials: M
authors.lastname: Sunayama
authors.forename: Miki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ando
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sugiura
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ideno
authors.forename: Akemi
authors.initials: A
authors.lastname: Shimada
authors.forename: Akira
authors.initials: A
authors.lastname: Nifuji
authors.forename: Masumi
authors.initials: M
authors.lastname: Abe
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D018797:Cell Cycle Proteins / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000276:immunology; D020869:Gene Expression Profiling; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000166:cytology / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D013724:Teratoma / Q000276:immunology / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C506693:Nohma protein, mouse; C487135:ZG-16 protein, mouse