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Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells
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Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells
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Journal Article
Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells
2013
Overview
Immune rejection may limit the therapeutic use of induced pluripotent stem cells (iPSCs); here, terminally differentiated mouse iPSCs are shown to generate negligible immune rejection in their host.
No immune reaction to iPSCs
Induced pluripotent stem cells (iPSCs) derived from a patient's own somatic cells could have great therapeutic potential. The hope is that iPSC-derived differentiated cells would avoid any immunogenic responses. In this study, Masumi Abe and colleagues assess the immunogenicity of skin and bone marrow tissues derived from a large set of isogenic mouse embryonic stem cell and iPSC lines. Their results are consistent with negligible immune rejection by the host.
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
1
,
2
. However, partial reprogramming and genetic instabilities in iPSCs
3
,
4
,
5
,
6
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
7
,
8
,
9
,
10
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
11
and implicated several causative genes. Nevertheless, some controversy has arisen regarding these findings
12
. 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Bone Marrow Cells - cytology
/ Bone Marrow Cells - immunology
/ Bone Marrow Transplantation - immunology
/ Cell Cycle Proteins - immunology
/ Cell Cycle Proteins - metabolism
/ Cell Differentiation - immunology
/ Cloning
/ Embryonic Stem Cells - cytology
/ Embryonic Stem Cells - immunology
/ Genomes
/ Humanities and Social Sciences
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - immunology
/ letter
/ Male
/ Membrane Proteins - immunology
/ Membrane Proteins - metabolism
/ Mice
/ Plasmids
/ Science
/ Skin Transplantation - immunology
/ Testing
/ Tissues
