Development of novel treatment for GVHD following hematopoietic cell transplantation using M2 macrophage

• Project/Area Number: 26461443
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• 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, 医学系研究科, 助教 (20456734)
• Co-Investigator(Renkei-kenkyūsha): TOYODA Hidemi 三重大学, 医学部附属病院, 講師 (60525327)
• Research Collaborator: HANAKI Ryo 三重大学, 医学部附属病院, 医員 (40780408)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 移植片対宿主病 / マクロファージ / 単球 / 造血細胞移植 / GVHD / ELISPOT法 / 慢性GVHD / 炎症性単球 / 抗炎症性単球 / 免疫組織染色法 / フローサイトメーター / 抗炎症性マクロファージ

Outline of Final Research Achievements

Treatment of chronic GVHD, which influences prognosis after hematopoietic cell transplantation, has not yet been established. We have previously demonstrated that anti-inflammatory monocytes produce IL-10 in chronic GVHD and are involved in the repair of damaged target organs. There are inflammatory M1 type and anti - inflammatory type M2 type in macrophages. Using this M2 macrophage, a novel treatment for GVHD has developed. Two types of macrophages M1 and M2 were induced by culturing them with cytokines of GM-CSF and M-CSF from mouse bone marrow cells. In murine GVHD model, M2 macrophages reduced lethal GVHD and improved survival rate. Future clinical application has been expected.

Research Products

• [Journal Article] Ewing Sarcoma of the Bone With EWS/FLI1 Translocation After Successful Treatment of Primary Osteosarcoma (2017)
  • Author(s): Yodoya, N. Iwamoto, S. Matsumine, A. Azuma, E. Toyoda, H. Miura, Y. Nakatani, K. Imai, H. Hirayama, M. Komada, Y.
  • Journal Title: J Pediatr Hematol Oncol Volume: 39 Issue: 1 Pages: 6-9
  • DOI: 10.1097/mph.0000000000000721
  • Peer Reviewed / Open Access
• [Journal Article] Disease Recurrence After Early Discontinuation of Eculizumab in a Patient With Atypical Hemolytic Uremic Syndrome With Complement C3 I1157T Mutation. (2016)
  • Author(s): Toyoda, H., Wada, H., Miyata, T., Amano, K., Kihira, K., Iwamoto, S., Hirayama, M., Komada, Y.
  • Journal Title: J Pediatr Hematol Oncol Volume: 38 Issue: 3 Pages: e137-e139
  • DOI: 10.1097/mph.0000000000000505
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neutrophils induced licensing of natural killer cells. (2015)
  • Author(s): 天野敬史郎、平山雅浩、東 英一、岩本彰太郎、駒田美弘
  • Journal Title: Mediators Inflamm Volume: ID747680 Pages: 1-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Long term follow up for childhood cancer surviver in Mie University Hospital (2017)
  • Author(s): 出口隆生、堀 浩樹、木平健太郎、平山雅浩
  • Organizer: 第120回日本小児科学会学術集会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都・港区）
  • Year and Date: 2017-04-14
• [Presentation] Hereditary tyrosinemia type 1 mimicking hepatoblastoma (2017)
  • Author(s): 栗原康輔、天野敬史郎、坂田佳子、木平健太郎、豊田秀実、岩本彰太郎、出口隆生、堀 浩樹、東 英一、平山雅浩
  • Organizer: 第120回日本小児科学会学術集会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都・港区）
  • Year and Date: 2017-04-14
• [Presentation] Significance of electrocardiogram for diagnosis of atrial septal defect (2017)
  • Author(s): 國米崇秀、澤田博文、三谷義英、大橋啓之、淀谷典子、中藤大輔、浅野舞、大槻祥一郎、早川豪俊、平山雅浩
  • Organizer: 第120回日本小児科学会学術集会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都・港区）
  • Year and Date: 2017-04-14
• [Presentation] Plaintive care of children with malignant brain tumors in our hospital (2016)
  • Author(s): 山下敦士、天野敬史郎、岡村聡、栗原康輔、鈴木尚史、杉浦勝美、花木良、坂田佳子、木平健太郎、豊田秀実、岩本彰太郎、出口隆生、堀 浩樹、東 英一、平山雅浩
  • Organizer: 第58回日本小児血液がん学会
  • Place of Presentation: 品川プリンスホテル（東京都・品川区）
  • Year and Date: 2016-12-15
• [Presentation] Interprofessional collaboration workshop for pediatric cancer care in Tokay-Hokuriku regional childhood cancer hospital (2016)
  • Author(s): 岩本彰太郎、奥野祐希、末藤美貴、井倉千佳、坂本由香、松原行志、河俣あゆみ、大森絵里子、谷口美佳、中西健二、前田多見、小田都紀子、福永稚子、松原貴子、高橋義行、平山雅浩
  • Organizer: 第58回日本小児血液がん学会
  • Place of Presentation: 品川プリンスホテル（東京都・品川区）
  • Year and Date: 2016-12-15
• [Presentation] Successful treatment of kaposiform hemangioendothelioma with disseminated intravascular coagulation using mTOR inhibitor in 2 cases. (2016)
  • Author(s): 森本真里、岡村聡、栗原康輔、鈴木尚史、杉浦勝美、花木良、坂田佳子、天野敬史郎、木平健太郎、岩本彰太郎、豊田秀実、出口隆生、堀 浩樹、東 英一、平山雅浩
  • Organizer: 第58回日本小児血液がん学会
  • Place of Presentation: 品川プリンスホテル（東京都・品川区）
  • Year and Date: 2016-12-15
• [Presentation] Efficacy of ultra-low dose AraC in DS-AMKL patient complicated by cardiopulmonary disease (2016)
  • Author(s): 森本真里、岩本彰太郎、山下敦士、大森あゆみ、岡村聡、栗原康輔、鈴木尚史、杉浦勝美、花木良、坂田佳子、天野敬史郎、木平健太郎、澤田博文、豊田秀実、出口隆生、堀 浩樹、東 英一、平山雅浩
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-10-13
• [Book] Biomarkers in Disease: General Methods in Biomarker Research and their Applications (2015)
  • Author(s): 平山雅浩、東 英一、駒田美弘
  • Total Pages: 1324
  • Publisher: Springer