Analysis of Therapeutic Potential of Monocytic Myeloid-derived Suppressor Cells in Cardiac Allotransplantation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18070
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Juntendo University
• Principal Investigator: Uchida Koichiro 順天堂大学, 健康総合科学先端研究機構, 准教授 (80648329)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 移植 / 拒絶反応 / 細胞治療 / 骨髄由来抑制性細胞

Outline of Final Research Achievements

Syngeneic and allogeneic bone marrow-derived MDSCs (BM-MDSCs) were induced and their effect on graft survival and suppressive capacity were analyzed. Moreover, we compared the ability of syngeneic monocytic MDSCs (Mo-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) to inhibit graft rejection and analyze the mechanisms of suppression.
Results Not only syngeneic but also allogeneic donor- or allogeneic third party-derived BM-MDSCs prolonged graft survival, although syngeneic BM-MDSCs inhibited anti-donor immune responses most effectively in vitro. Mo-MDSCs, rather than PMN-MDSCs, were responsible for immune suppression through inducible nitric oxide synthase (iNOS), and expanded naturally occurring thymic originated Treg (nTreg) in vitro. Adoptive transfer of Mo-MDSCs, but not PMN-MDSCs, prolonged graft survival and increased Treg infiltration into the graft heart.

Free Research Field

移植免疫

Academic Significance and Societal Importance of the Research Achievements

単球系の骨髄由来抑制細胞のターゲットとした新たな免疫抑制治療の効果メカニズムが解明された。これらにより、副作用の強い薬剤の全身投与ではなく、抑制性細胞治療という炎症部位を選択的に制御できる方法論の治療コンセプトを確立することができた。
この細胞療法は、制御性T細胞治療のように、レシピエントのMHCを合わせなくても、投与可能であり、効果を発揮する。また骨髄細胞は、比較的容易に採取可能であり、将来の安定供給可能な体制を構築しやすい。