IPS cells but not their hematopoietic derivatives are immunogenic in the autologous recipient (P2210)

Abstract

Abstract Induced pluripotent stem (iPS) cells are derived by reprogramming somatic cells, mostly fibroblasts. Since these cells can be generated from patients, the asuumption is that when the cells are transplanted back to the donor, immunological rejection can be ruled out. However, recently a manuscript showed that in fact iPS cells are rejected by "self". This result was unexpected and might significantly impact the use of iPS cells clinically. Here, we hypothesized that iPS cells are immunogenic to "self" because they express carcinogenic/embryonic antigens that are not expressed on somatic cells. Consequently, we argued that iPS cell derivatives lose the ability to express these antigens and should therefore be non-immunogenic to "self". To address this question, 129SvJ iPS cells or 129SvJ ES cells were subcutaneously injected in 129 SvJ mice, respectively. After 4 weeks, teratomas were visible in mice that had been injected with ES cells but not in mice injected with iPS cells, suggesting that iPS cells had been rejected. iPS cells were then used to derive hematopoietic progenitor cells. When these cells were infused intravenously, they easily induced long-term mixed chimerism, suggesting that non-differentiated iPS cells but not their derivatives are immunogenic to"self". Interestingly, ES cells were also rejected in" iPS-sensitized" but not in naive mice. Rejection was mediated by T cells.