| Project/Area Number |
17K09898
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Obara Naoshi 筑波大学, 医学医療系, 准教授 (70422178)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 造血不全 / Nestin / 造血支持細胞 / GFAP / 骨髄異形成症候群 / 赤芽球島 / 造血微小環境 / 炎症性貧血 / IL-6 / マクロファージ / Notchシグナル / Rbpj / 分化障害 / 赤芽球 |
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| Outline of Final Research Achievements |
Various types of hematopoietic supporting cells have been reported. Recently, Nestin-expressing cells, which are neural stem-cell markers, and Schwann cells were identified in the bone marrow.
We analyzed Nestin-expressing stromal cells (NESCs) and glial fibrillary acidic protein (GFAP)-expressing cells, which are Schwann cell markers, in myelodysplastic syndrome (MDS). We found a marked increase in the NESC levels in MDS with fibrosis (MDS-F) at a high frequency (9/19; 47.4%), but not in MDS without fibrosis (0/26; 0%). In eight of the nine (88.9%) MDS-F cases with elevated NESCs, a majority of NESCs also expressed GFAP, with an additional increase in GFAP single-positive cells. Furthermore, in seven of the nine cases, a prominent structure was observed characterized by neurofilament heavy chain staining surrounded by NESCs with GFAP expression. This structure may represent peripheral nerve axons surrounded by Schwann cells and could be associated with the pathophysiology of MDS-F.
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| Academic Significance and Societal Importance of the Research Achievements |
骨髄異形成症候群（MDS）をはじめとした造血不全は最も治療困難な疾患の一つであり、輸血依存となることも多く、医療のみならず社会的・医療経済上も影響が大きい疾患である。メチル化阻害剤などが試みられているが、いまだ根治的治療については造血幹細胞移植以外ないのが現状であり、高齢者・ドナーのいない患者などでは治療に苦慮することも多い。
今回、我々は繊維化を伴うMDSについて、造血支持細胞の異常が関与していることを示した。また、マウスモデルにおいても造血支持細胞の異常によって赤血球造血が障害されることを示した。今後、新たな予後因子の決定・繊維化をターゲットにした新規治療法の開発などへの展開が期待できる。
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