Elucidation of pathophysiology and novel treatment of chronic GVHD after transplantation using genetically modified mouse C / EBPb

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08836
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Mie University
• Principal Investigator: Hirayama Masahiro 三重大学, 医学系研究科, 教授 (90293795)
• Co-Investigator(Kenkyū-buntansha): 岩本 彰太郎 三重大学, 医学部附属病院, 准教授 (20456734)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: GVHD / 造血細胞移植 / マクロファージ / 単球

Outline of Final Research Achievements

Graft-versus-host disease (GVHD) is an important complication of hematopoietic cell transplantation. In recent years, macrophages (MΦ) have been divided into two types: M1 (inflammatory) and M2 (anti-inflammatory). Therefore, we examined an GVHD suppression effect of M2Φ. First, we performed in inducing M1 (CD38 positive) and M2 (CD206 positive) by culturing bone marrow cells in GM-CSF and/or M-CSF. By using the murine GVHD model, M2Φ significantly suppressed GVHD and improved survival rate. Improvement was also confirmed in the clinical and pathological GVHD scores. In organs in which GVHD was suppressed, M2Φ was predominantly infiltrated. After all, M2Φ cell therapy is expected to suppress the GVHD on hematopoietic cell transplantation.

Free Research Field

血液腫瘍分野

Academic Significance and Societal Importance of the Research Achievements

造血細胞移植は難治性血液腫瘍性疾患の治療で有効な治療法となっている。その中で、移植片対宿主病（GVHD）は移植後の極めて重要な合併症である。近年、マクロファージの免疫作用が注目される中、この細胞を用いてGVHDを克服するための細胞療法をマウスモデルで開発した。今後、ヒト、臨床に応用することで、学術的および社会的な意義は高いと考える。