Histopathological analysis of bone marrow remodeling process after hematopoietic stem cell transplantation and identification of cells responsible for engraftment failure

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16585
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Osaka University
• Principal Investigator: Kurashige Masako 大阪大学, 医学系研究科, 特任助教(常勤) (10836422)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 骨髄 / ニッチ / 造血幹細胞移植

Outline of Final Research Achievements

Histopathological analysis of bone marrow after hematopoietic stem cell transplantation (HSCT) revealed that hematopoietic cells proliferate in a unique manner during the normal engraftment process. The cellularity of the bone marrow showed different secular changes depending on the hematopoietic stem cell source. After confirming that the human counterpart of mouse CAR cells (hCAR cells) can be histologically identified with EBF3 and CD271, we performed in-situ chimerism analysis of hCAR cells after HSCT in cases of normal engraftment and revealed that almost all hCAR cells after HSCT were derived from the recipient. In situ gene expression analysis of patients with myelofibrosis revealed that CXCL12 expression in hCAR cells was significantly elevated after HSCT compared with preconditioning.

Free Research Field

血液病理

Academic Significance and Societal Importance of the Research Achievements

ヒト造血幹細胞移植後の骨髄再構築過程を組織学的に解析した研究は極めて少なく、本研究では造血様式や細胞密度の変化のみでなく、移植ソースによる違いや組織マクロファージや造血幹細胞ニッチの主たる構成細胞であるCAR細胞のキメリズムの変化まで含めて明らかにした。また、少数例であるが骨髄線維症患者では移植後にCAR細胞のCXCL12発現レベルが上昇することを示した。これらの結果は血液病理学のみでなく移植医療においても重要な知見になると考えられる。