Repairing of heamatopoietic niche in bone marrow after X-ray irradiation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09867
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Keio University
• Principal Investigator: Mise-Omata Setsuko 慶應義塾大学, 医学部(信濃町), 特任助教 (00269052)
• Co-Investigator(Kenkyū-buntansha): 青木 和広 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (40272603)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 骨代謝 / 脂肪細胞 / 造血幹細胞ニッチ / マクロファージ

Outline of Final Research Achievements

Lethal X-ray radiation before HSC transplantation often induce the bone loss in the patients. We found a correlation between bone loss and the impairment of hematopoietic environment induced by hyper-differentiation of adipocytes, by using two different strains of mice, one is RelA-deficient mouse suffering from severe bone loss and the other is Spred1/Spred2 double knockout mouse which increases its bone mass after HSC transplantation. The adipocytes differentiated in the bone morrow after X-ray radiation were rapidly deprived in the Spred DKO mice and in these mice hematopoietic ability was enhanced compared with wild type mice. In contrast, the number of adipocytes markedly increased and hematopoietic ability was impaired in RelA-deficient mice. Inflammatory macrophages are highly differentiated in RelA-deficient mice, it may cause the over-differentiation of adipocytes.

Free Research Field

造血幹細胞移植

Academic Significance and Societal Importance of the Research Achievements

造血幹細胞移植は、白血病や再生不良性貧血などで病気からの治癒を目指すことのできる唯一の治療法である。造血幹細胞移植を行う前には、患者自身の造血細胞を死滅させるために致死量のX線照射や抗がん剤投与などが行われるが、X線照射を受けた患者のなかには、骨量が減少し治療後のQOLが著しく低下するケースがある。本研究成果によってX線照射は脂肪細胞の分化を引き起こし、その分化が強いと骨形成や造血が低下し、その反対に脂肪細胞が少ないと骨形成や造血が亢進することを明らかにした。本研究成果は、造血幹細胞移植後の患者のQOLの向上に一助を与えるものと考える。