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鎌谷　智紀 (カマタニ　トモキ)

遺伝子病制御研究所　病態研究部門助教

研究者基本情報

■ 学位
  • 博士（医学）, 北海道大学, 2025年06月
■ URL
researchmap URLホームページURL■ ID 各種
研究者番号
  • 01026021
ORCID IDJ-Global ID■ 研究キーワード・分野
研究キーワード
  • iPS細胞
  • 免疫学
  • 移植
研究分野
  • ライフサイエンス, 発生生物学, 再生医学
  • ライフサイエンス, 免疫学, 腫瘍免疫学
  • ライフサイエンス, 免疫学, 移植免疫学

経歴

■ 経歴
経歴
  • 2025年07月 - 現在
    北海道大学, 遺伝子病制御研究所 免疫生物分野, 助教, 日本国
学歴
  • 2025年06月, 北海道大学, 医学院 医学専攻 博士課程, 日本国

研究活動情報

■ 受賞
  • 2025年03月, 2025年日本再生医療学会奨励賞（基礎部門）
  • 2024年12月, 2024年Ursula and Fritz Melchers Travel Award
  • 2024年12月, 第53回日本免疫学会学術集会 ベストプレゼンテーション賞
  • 2023年11月, 2023年度日本臓器保存生物医学会 研究奨励賞
  • 2023年03月, 2023年度（前期）Tadamitsu Kishimoto International Travel Award
  • 2021年11月, 第47回日本臓器保存生物医学会学術集会 学会賞
■ 論文
  • iPS細胞の移植への応用
    鎌谷智紀; 清野研一郎
    臨床免疫・アレルギー科, 85, 4, 405, 408, 2026年04月, ［招待有り］, ［筆頭著者, 責任著者］
    日本語, 研究論文（学術雑誌）
  • iPS細胞を用いた移植免疫寛容の誘導とメカニズム解析
    鎌谷 智紀; 清野 研一郎
    Organ Biology, 32, 2, 113, 117, 2025年09月, ［招待有り］, ［筆頭著者］
    日本語, 研究論文（学術雑誌）
  • iPSCs engrafted in allogeneic hosts without immunosuppression induce donor-specific tolerance to secondary allografts.
    Tomoki Kamatani; Reiko Kimura; Satoshi Ikeda; Makoto Inoue; Ken-Ichiro Seino
    Proceedings of the National Academy of Sciences of the United States of America, 122, 11, e2413398122, 2025年03月18日, ［査読有り］, ［筆頭著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, Currently, most cell or tissue transplantations using induced pluripotent stem cells (iPSCs) are anticipated to involve allogeneic iPSCs. However, the immunological properties of iPSCs in an allogeneic setting are not well understood. We previously established a mouse transplantation model of MHC-compatible/minor antigen-mismatched combinations, assuming a hypoimmunogenic iPSC-setting. Here, we found that iPSCs subcutaneously inoculated into MHC-compatible allogeneic host mice resisted rejection and formed teratomas without immunosuppressant administration. Notably, when skin grafts were transplanted onto hosts more than 40 d after the initial iPSCs inoculation, only the skin of the same strain as the initial iPSCs was engrafted. Therefore, donor-specific immune tolerance was induced by a single iPSC inoculation. Diverse analyses, including single-cell RNA-sequencing after transplantation, revealed an increase in regulatory T cell (Treg) population, particularly CD25+ CD103+ effector Tregs within the teratoma and skin grafts. The removal of CD25+ or Foxp3+ cells suppressed the increase in effector Tregs and disrupted graft acceptance, indicating the importance of these cells in the establishment of immune tolerance. Within the teratoma, we observed an increase in TGF-β2 levels, suggesting an association with the increase in effector Tregs. Our results provide important insights for future applications of allogeneic iPSC-based cell or tissue transplantation.
  • Induced pluripotent stem cell-derived hematopoietic stem and progenitor cells induce mixed chimerism and donor-specific allograft tolerance.
    Tomoki Murata; Naoki Hama; Tomoki Kamatani; Akihiro Mori; Ryo Otsuka; Haruka Wada; Ken-Ichiro Seino
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 23, 9, 1331, 1344, 2023年09月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, In transplantation using allogeneic induced pluripotent stem cells (iPSCs), strategies focused on major histocompatibility complexes were adopted to avoid immune rejection. We showed that minor antigen mismatches are a risk factor for graft rejection, indicating that immune regulation remains one of the most important issues. In organ transplantation, it has been known that mixed chimerism using donor-derived hematopoietic stem/progenitor cells (HSPCs) can induce donor-specific tolerance. However, it is unclear whether iPSC-derived HSPCs (iHSPCs) can induce allograft tolerance. We showed that 2 hematopoietic transcription factors, Hoxb4 and Lhx2, can efficiently expand iHSPCs with a c-Kit+Sca-1+Lineage- phenotype, which possesses long-term hematopoietic repopulating potential. We also demonstrated that these iHSPCs can form hematopoietic chimeras in allogeneic recipients and induce allograft tolerance in murine skin and iPSC transplantation. With mechanistic analyses, both central and peripheral mechanisms were suggested. We demonstrated the basic concept of tolerance induction using iHSPCs in allogeneic iPSC-based transplantation.
  • Induction of allograft tolerance by adoptive transfer of donor B cells: an immune regulatory strategy for transplantation using MHC-matched iPS cells.
    Tomoki Murata; Ryo Otsuka; Airi Sasaki; Tomoki Kamatani; Haruka Wada; Hisashi Yamakawa; Yoshinori Hasegawa; Ken-Ichiro Seino
    International immunology, 35, 7, 327, 338, 2023年07月07日, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, For cellular or tissue transplantation using induced pluripotent stem cells (iPSCs), from the viewpoint of time and economic cost, the use of allogeneic ones is being considered. Immune regulation is one of the key issues in successful allogeneic transplantation. To reduce the risk of rejection, several attempts have been reported to eliminate effects of the major histocompatibility complex (MHC) on the iPSC-derived grafts. On the other hand, we have shown that minor antigen-induced rejection is not negligible even when the MHC's impact is mitigated. In organ transplantation, it is known that donor-specific transfusion (DST) can specifically control immune responses to the donor. However, whether DST could control the immune response in iPSC-based transplantation was not clarified. In this study, using a mouse skin transplantation model, we demonstrate that infusion of donor splenocytes can promote allograft tolerance in the MHC-matched but minor antigen-mismatched conditions. When narrowing down the cell types, we found that infusion of isolated splenic B cells was sufficient to control rejection. As a mechanism, the administration of donor B cells induced unresponsiveness but not deletion in recipient T cells, suggesting that the tolerance was induced in the periphery. The donor B cell transfusion induced allogeneic iPSC engraftment. These results suggest for the first time a possibility that DST using donor B cells could induce tolerance against allogeneic iPSC-derived grafts.
  • MHC型一致他家iPS細胞由来組織移植に有効な免疫抑制剤併用プロトコールの構築
    鎌谷 智紀; 清野 研一郎
    Organ Biology, 29, 2, 133, 137, (一社)日本臓器保存生物医学会, 2022年07月, ［招待有り］, ［筆頭著者］
    日本語, In transplantation medicine using iPS cells, it is planned to use off-the-shelf iPS cells derived from allogeneic iPS cells for rapid and low-cost utilization of clinical-grade cells. To reduce the possibility of rejection, it is designed to use HLA-homozygous iPS cells for the off-the-shelf product, and several lines have been established for future HLA-matched transplants. This article describes our efforts to control rejection in HLA-matched allogeneic iPS cell-based transplantation, focusing on establishing immunosuppression protocols.
  • Evaluation of immunosuppression protocols for MHC-matched allogeneic iPS cell-based transplantation using a mouse skin transplantation model.
    Tomoki Kamatani; Ryo Otsuka; Tomoki Murata; Haruka Wada; Takeshi Takahashi; Akihiro Mori; Soichiro Murata; Hideki Taniguchi; Ken-Ichiro Seino
    Inflammation and regeneration, 42, 1, 4, 4, 2022年02月02日, ［査読有り］, ［筆頭著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Off-the-shelf major histocompatibility complex (MHC)-matched iPS cells (iPSC) can potentially initiate host immune responses because of the existence of numerous minor antigens. To suppress allo-immune responses, combination of immunosuppressants is usually used, but its efficacy to the allogeneic iPSC-based transplantation has not been precisely evaluated. METHODS: Three transplantation models were used in this study; MHC-matched, minor antigen-mismatched mouse skin or iPSC-graft transplantation, and fully allogeneic human iPSC-derived liver organoid transplantation in immune-humanized mice. The recipients were treated with triple drugs combination (TDC; tacrolimus, methylprednisolone, and mycophenolate mofetil) or co-stimulatory molecule blockade (CB) therapy with some modifications. Graft survival as well as anti-donor T and B cell responses was analyzed. RESULTS: In the mouse skin transplantation model, immunological rejection caused by the minor antigen-mismatch ranged from mild to severe according to the donor-recipient combination. The TDC treatment could apparently control the mild skin graft rejection when combined with a transient T cell depletion, but unexpected anti-donor T or B cell response was observed. On the other hand, CB therapy, particularly when combined with rapamycin treatment, was capable of attenuating both mild and severe skin graft rejection and allowing them to survive long-term without any unfavorable anti-donor immune responses. The efficacy of the CB therapy was confirmed in both mouse and human iPSC-derived graft transplantation. CONCLUSIONS: The findings suggest that the CB-based treatment seems suitable to well manage the MHC-matched allogeneic iPSC-based transplantation. The TDC-based treatment may be also used to suppress the rejection, but screening of its severity prior to the transplantation seems to be needed.
■ その他活動・業績
■ 所属学協会
  • 日本がん免疫学会
  • 日本臓器保存生物医学会
  • 日本炎症・再生医学会
  • 日本再生医療学会
  • 日本移植学会
  • 日本免疫学会
■ 共同研究・競争的資金等の研究課題
■ 産業財産権
  • 免疫寛容誘導組成物
    特許権, 清野研一郎; 鎌谷智紀, 国立大学法人北海道大学
    特願2023-075353, 2023年04月30日