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Generation of dendritic cells and macrophages from human induced pluripotent stem cells aiming at cell therapy

Gene Therapy volume 18, pages 874–883 (2011)Cite this article

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Abstract

This report describes generation of dendritic cells (DCs) and macrophages from human induced pluripotent stem (iPS) cells. iPS cell-derived DC (iPS-DC) exhibited the morphology of typical DC and function of T-cell stimulation and antigen presentation. iPS-DC loaded with cytomegalovirus (CMV) peptide induced vigorous expansion of CMV-specific autologous CD8+ T cells. Macrophages (iPS-MP) with activity of zymosan phagocytosis and C5a-induced chemotaxis were also generated from iPS cells. Genetically modified iPS-MPs were generated by the introduction of expression vectors into undifferentiated iPS cells, isolation of transfectant iPS cell clone and subsequent differentiation. By this procedure, we generated iPS-MP expressing a membrane-bound form of single chain antibody (scFv) specific to amyloid β (Aβ), the causal protein of Alzheimer’s disease. The scFv-transfectant iPS-MP exhibited efficient Aβ-specific phagocytosis activity. iPS-MP expressing CD20-specific scFv engulfed and killed BALL-1 B-cell leukemia cells. Anti-BALL-1 effect of iPS-MP in vivo was demonstrated in a xeno-transplantation model using severe combined immunodeficient mice. In addition, we established a xeno-free culture protocol to generate iPS-DC and iPS-MP. Collectively, we demonstrated the possibility of application of iPS-DC and macrophages to cell therapy.

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Acknowledgements

We thank Dr H Miyoshi for a lentivirus vector system and Dr H Niwa for a mammalian expression vector pCAGGS-IRES-PuroR. This work was supported in part by Grants-in-Aid 18014023, 19591172 and 19059012 from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan, the Program of Founding Research Centers for Emerging Infectious Diseases launched as a project commissioned by MEXT, Research Grant for Intractable Diseases from Ministry of Health and Welfare, Japan, grants from Japan Science and Technology Agency (JST), the Uehara Memorial Foundation, and the Takeda Science Foundation.

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Authors and Affiliations

  1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    S Senju, M Haruta, K Matsumura, Y Matsunaga, S Fukushima, T Ikeda, K Takamatsu, A Irie & Y Nishimura

  2. CREST, Japan Science and Technology Agency, Kawaguchi, Japan

    S Senju, M Haruta, K Matsumura, Y Matsunaga, S Fukushima, T Ikeda, K Takamatsu & A Irie

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  1. S Senju
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Correspondence to S Senju.

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Senju, S., Haruta, M., Matsumura, K. et al. Generation of dendritic cells and macrophages from human induced pluripotent stem cells aiming at cell therapy. Gene Ther 18, 874–883 (2011). https://doi.org/10.1038/gt.2011.22

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