Cellular Engineering of the Immune System Using Pluripotent Stem Cells and Antibody Technolog

Our lab integrates stem cell biology and immunology to engineer functional immune cells for both basic research and therapeutic application. We have developed in vitro systems to generate platelets and T cells from human pluripotent stem cells (PSCs), and demonstrated that antigen-specific T cells can be rejuvenated via iPSC reprogramming and redifferentiation—enabling the production of cytotoxic T cells with preserved TCR specificity. Building on these technologies, we are also generating genetically modified immune cells, including iPSC-derived CAR-T and CAR-macrophages, to explore new immunotherapeutic strategies. Our expertise in antibody generation and protein engineering further allows us to design custom receptors and refine cellular functions. These multidisciplinary efforts aim to establish a versatile platform for programmable, stem cell–derived immune effectors.

Representative publications:

1. Takayama N, Nishikii H, Usui J, Tsukui H, Sawaguchi A, Hiroyama T, Eto K. and Nakauchi H. (2008). Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors. Blood. 111:5298-306. "PMID": 18388179.

2. Nishimura T, Kaneko S, Kawana-Tachikawa A, Tajima Y, Goto H, Zhu D, Nakayama-Hosoya K, Iriguchi S, Uemura Y, Shimizu T, Takayama N, Yamada D, Nishimura K, Ohtaka M, Watanabe N, Takahashi S, Iwamoto A, Koseki H, Nakanishi M, Eto K, Nakauchi H (2013). Generation of rejuvenated antigen- specific T cells by reprogramming to pluripotency and redifferentiation. Cell Stem Cell. 12(1):114-126. PMID: 23290140

3. Nakamura S, Takayama N, Hirata S, Seo H, Endo H, Ochi K, Fujita K, Koike T, Harimoto K, Dohda T, Watanabe A, Okita K, Takahashi N, Sawaguchi A, Yamanaka S, Nakauchi H, Nishimura S, Eto K (2014). Expandable megakaryocyte cell lines enable clinically applicable generation of platelets from human induced pluripotent stem cells. Cell Stem Cell. 14(4):535-548. PMID: 24529595

4. Furukawa Y, Ishii M, Ando J, Ikeda K, Igarashi KJ, Kinoshita S, Azusawa Y, Toyota T, Honda T, Nakanishi M, Ohshima K, Masuda A, Yoshida E, Kitade M, Porteus M, Terao Y, Nakauchi H, Ando M. (2023). iPSC-derived hypommunogenic tissue resident memory T cells mediate robust anti-tumor activity against cervical cancer. Cell Rep Med. 4(12):101327. PMID: 380919