A novel pathway of megakaryopoiesis after cord blood transplantation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09946
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: Kurita Naoki 筑波大学, 医学医療系, 講師 (30555561)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 巨核球前駆細胞 / 臍帯血移植 / トロンボポエチン

Outline of Final Research Achievements

Cord blood (CB) is a promising alternative source for patients without HLA-matched donors. However, delayed platelet recovery after CB transplantation (CBT) is yet to be solved. We focused on megakaryopoiesis after CBT through megakaryocytic progenitors (MKP), which is novel differentiation pathway. We aimed to clarify the mechanism which intra-bone injection of CB and thrombopoietin receptor agonist (TPO-RA) promotes platelet recovery via MKP pathway. We found that the number of MKP was increased after intra-bone injection of CB using mouse models. TPO, which is indispensable for differentiation of MKP, was expressed on stromal cells in the bone marrow. Analysis of the nation-wide database of hematopoietic stem-cell transplantation revealed that the survival of patients who achieved platelet recovery after CBT was comparable to that after bone marrow transplantation. Based on these findings, we are also conducting a clinical trial of TPO-RA administration in the early phase after CBT.

Free Research Field

造血幹細胞移植

Academic Significance and Societal Importance of the Research Achievements

本邦の非血縁者間移植の約半数を臍帯血移植が占め，世界で最も臍帯血移植が盛んである．しかし臍帯血移植では，血小板減少期間の遷延により出血性合併症のリスクが高く，頻回の輸血を要することから入院の長期化，医療費の増加に繋がりうる．本研究により臍帯血骨髄内移植，臍帯血移植後早期のトロンボポエチン受容体作動薬投与の血小板早期回復に対する効果が示せ，巨核球前駆細胞を介した血小板造血促進の理論的背景を示すことができれば，臍帯血移植の唯一の欠点である移植後の血球回復遅延の問題が克服できる可能性がある．その結果，臍帯血移植成績の向上，臍帯血移植適応の拡大により，移植医療に対して大きく貢献できる．