Harnessing the single-cell biology and biomarker involving in the therapeutic response of patients with severe acute graft-versus-host disease undergoing mesenchymal stem cell transfusion

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16605
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yokoyama Kazuaki 東京大学, 医科学研究所, 助教 (00647498)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 造血幹細胞移植 / 急性移植片対宿主病 / 1細胞RNAシーケンス解析 / 間葉系幹細胞

Outline of Final Research Achievements

Severe acute graft-versus-host disease (aGVHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (alloSCT) for treatment of hematological disease. This is true for the patients with steroid-refractory aGVHD.Human mesenchymal stem cells (MSC)transfusion represents one of the most effective salvage therapy for patients with steroid-refractory aGVHD. However, the main problem of MSC therapy is that the there is no therapeutic biomarker.To this aim, we performed single cell RNA analysis of the peripheral blood mononuclear cells before and after MSC infusion from patients with aGVHD. As a result, we found the candidate aGVHD-regulatory cells with their transcriptome with putative biomarkers, A and B. This will be able to elucidate aGVHD regulatory cells, which will lead to establishment of therapeutic biomarkers for patients with aGVHD undergoing MSC transfusion.

Free Research Field

血液腫瘍

Academic Significance and Societal Importance of the Research Achievements

造血幹細胞移植は、急性白血病などの難治性血液疾患の根治的治療法の一つとして確立されているが、合併症として急性移植片対宿主病(aGVHD)が課題である。を克服する事に繋がり得る。近年、間葉系幹細胞(MSC)療法が注目されているがその生体内での作用機序とバイオマーカーが不明である。そこで本研究では、MSC療法を受けたaGVHD患者を対象 とした、治療前後の末梢血免疫細胞の1細胞RNAシーケンス解析を行うことで、MSCが誘導していると考えられる、未知のaGVHD制御に関わる免疫細胞集団候補とバイオマーカ候補としてA,Bを同定した。これによりMSCの治療反応バイオマーカーの確立に繋がる。