To Be Immunogenic or Not? It Is Not a Question Anymore

In 2006, Japanese scientist Shinya Yamanaka gained the lead with iPS technology induced pluripotent stem cells (iPSC). Since then, the technology has been seen as the hope of cell therapy. It is widely believed that the patient's own cells from iPSC differentiation will not cause immune rejection after transplantation back into his body.

But in 2011, Yang Xu, professor of the University of California, San Diego, published an article in Nature, that presents a challenge to this idea. His research team used mouse skin cells to generate the iPSCs and transplanted it into genetically identical mice. They found that the mice did not form teratomas after transplantation, but those transplanted with ESCs using the same method formed teratomas. Professor Xu believed that was because the iPSC was under attack and rejection of the immune system in mice.

In a while, the security problem of iPS has caused a great controversy, but also become the focus of researchers. However, in some subsequent studies, researchers got conflicting conclusions, and it seemed that some iPSC-derived cells had no immune rejection.

For example, Japan's National Institute of Radiology researchers separately fused iPSC and ESC with mouse embryos to develop into chimeric mice. They then transplanted skin and bone marrow cells of these mice into genetically identical mice, but did not find any strong immune response. In addition, researchers at Boston University School of Medicine used mice iPSC to differentiate into three different cell lines, and transplanted these cells into mouse with the same genes. It did not trigger any strong immune responses either.

In order to clarify the immunogenicity of autologous human iPSC (hiPSC)-derived cells, Professor Xu led the research team to build a more powerful research model—a humanized mouse model with a functional human immune system in mice.

They demonstrate that most teratomas formed by autologous integration-free hiPSCs exhibit local infiltration of antigen-specific T cells and associated tissue necrosis, indicating immune rejection of certain hiPSC-derived cells.

Their studies suggest that autologous hiPSC-derived smooth muscle cells (SMCs) show a high immunogenicity, while autologous hiPSC-derived retinal pigment epithelium (RPE) is immune tolerated even in non-ocular locations. These researchers also note that, this differential immunogenicity is due in part to abnormal expression of immunogenic antigens in hiPSC-derived SMCs, but not in hiPSC-derived RPEs. Their findings support show that developing hiPSC-derived RPEs for treating macular degeneration is entirely feasible.

Source: Humanized Mice Reveal Differential Immunogenicity of Cells Derived from Autologous Induced Pluripotent Stem Cells, Cell Stem Cell