The abnormalities of Haematopoietic supporting cells and impaired erythroblast island formation in bone marrow failure disease.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08365
• 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: University of Tsukuba
• Principal Investigator: Obara Naoshi 筑波大学, 医学医療系, 教授 (70422178)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: bone marrow failure / Nestin / GFPD / aplastic anemia

Outline of Final Research Achievements

In this study, analyses were performed mainly on bone marrow biopsy specimens in disease groups with bone marrow failure and pancytopenia, such as myelodysplastic syndromes, aplastic anaemia and myelofibrosis. Analysis of Nestin-positive cells in bone marrow, which may support haematopoiesis, was attempted mainly using immunostaining.
We found a marked increase in Nestin-positive cells in the bone marrow of patients with MDS with fibrosis. In addition, when macrophages derived from MDS patients were collected and mixed with control erythroblasts in an erythroblast island reconstruction experiment, the number of erythroblast islands tended to be lower than when control macrophages were used. There was also a tendency for fewer erythroblasts to adhere to the macrophages.In some MDS, In some MDS, anemia via impaired erythroblast formation is present.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

骨髄における神経外胚葉形細胞の役割とその異常による造血障害の可能性：骨髄中で、神経外胚葉関連と考えられるNestin陽性の造血支持細胞の存在が確認されており、造血幹細胞ニッチを形成していることが報告されている。これらの機序については主にマウスモデルからの解明されてきたが、実際のヒト疾患でこれらの造血支持細胞が病態に関与しているかどうかは明らかではなかった。本研究では、一部の造血不全疾患でNestin陽性の造血支持細胞が病態に関与している可能性をヒトサンプルの解析から明らかにした。また、貧血の要因として、赤芽球を支持しているマクロファージの異常が関与している可能性が示された。。