Induction of macrophage-Like immunosuppressive cells from mouse ES cells that contribute to prolong allogeneic graft survival

Hiroya Kudo, Haruka Wada, Hajime Sasaki, Hyuma Tsuji, Ryo Otsuka, Muhammad Baghdadi, Satoshi Kojo, Tatsuya Chikaraishi, Ken Ichiro Seino

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8 Citations (Scopus)

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 donorrecipient 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 ESCsderived 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.

Original languageEnglish
Article numbere111826
JournalPloS one
Volume9
Issue number10
DOIs
Publication statusPublished - Oct 30 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Kudo, H., Wada, H., Sasaki, H., Tsuji, H., Otsuka, R., Baghdadi, M., Kojo, S., Chikaraishi, T., & Seino, K. I. (2014). Induction of macrophage-Like immunosuppressive cells from mouse ES cells that contribute to prolong allogeneic graft survival. PloS one, 9(10), [e111826]. https://doi.org/10.1371/journal.pone.0111826