Verification of avoidance of radiation-induced acute injury by adipose stem cell (ADSC) transplantation -Focus on bone marrow damage-

• Project/Area Number: 18K11649
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Akira OOTSUYAMA 産業医科大学, 医学部, 准教授 (10194218)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 脂肪幹細胞 / ADSC / 放射線骨髄障害 / 再生医療 / 組織再生 / 幹細胞移植 / 放射線障害 / 放射線障害回避 / 放射線 / 骨髄障害

Outline of Final Research Achievements

We examined whether transplantation of adipose stem cells (ADSCs) into X-ray-exposed mice could recover from a radiation-induced acute injury, especially bone marrow damage, similar to bone marrow transplantation. 1X10＾6 ASCS derived from subcutaneous adipose tissue from male mice were intravenously transplanted 6.5 Gy C57BL/6 female mice exposed to X-rays. The changes in survival rate with time were compared with those of non-irradiated mice. After transplantation of fluorescently stained ADSCs, major organs were sampled with time for histological observation and DNA was extracted and PCR was performed to determine the expression of the male-marker gene SSTY2.
The survival rate of the transplanted group was 30% higher than that of the non-transplanted group at about 20 days after irradiation, demonstrating recovery of radiation-induced bone marrow damage by ADSCs. Histological observation and PCR results showed that the transplanted cells accumulated in the lung and spleen.

Academic Significance and Societal Importance of the Research Achievements

脂肪幹細胞は多能性幹細胞であり、多方面の再生医療の様々な組織の再生に用いられている。ただし、脂肪幹細胞に造血支持能力はあるが骨髄移植の代替になるという報告は無い。本研究の成果は、HLA適合や採集量が少ない等の問題がある骨髄細胞移植使用に対し、そのような制約が少ない脂肪幹細胞が、放射線急性骨髄障害を回復させうる能力があることを証明したことに学術的意義がある。また、社会的には事故原子炉の撤去など高線量被曝の可能性がある作業現場が長期にわたり存在する現状をふまえ、緊急被曝医療の一端として脂肪幹細胞の移植が、高線量被曝時の急性骨髄障害の忌避のために有効な手段となれば、社会的意義も大きいと考えている。

Research Products

• [Journal Article] Life-Prolonging Effects of Adipose Tissue-Derived Stem Cell Transplantation into Mice Exposed to a Lethal Dose of X-Rays (2021)
  • Author(s): Akira Ootsuyama
  • Journal Title: Journal of UOEH Volume: 43 Issue: 1 Pages: 25-31
  • DOI: 10.7888/juoeh.43.25
  • NAID: 130007995226
  • ISSN: 0387-821X, 2187-2864
  • Year and Date: 2021-03-01
  • Peer Reviewed / Open Access
• [Presentation] Transplantation of adipose-derived stem cell (ADSCs) plus bone marroe to mice after whole body X-ray-irradiation (2020)
  • Author(s): Akira OOTSUYAMA
  • Organizer: 日本放射線影響学会 第63回大会 (福島)
• [Presentation] Effects of adipose tissue-derived stem cell transplantation in whole-body X-ray irradiated mice -Destination of transplantrd cells- (2019)
  • Author(s): Akira OOTSUYAMA
  • Organizer: 日本放射線影響学会 第62回大会 (京都)
• [Presentation] 脂肪幹細胞(ADSC)による放射線障害の軽減作用 III (2019)
  • Author(s): 大津山 彰
  • Organizer: 第56回 放射線影響懇話会 (熊本)
• [Presentation] Effect of adipose-derived stem cell (ADSC) transplantation to reduce whole body X ray damage in mice (2019)
  • Author(s): Akira OOTSUYAMA
  • Organizer: 16th International Congress of Radiation Research (Manchester, England)
  • Int'l Joint Research
• [Presentation] 脂肪幹細胞(ADSC)による放射線障害の軽減作用 II (2018)
  • Author(s): 大津山 彰
  • Organizer: 第55回放射線影響懇話会
• [Presentation] X線被ばくマウスに対する脂肪組織由来幹細胞(ADSC)移植の放射線障害軽減効果 (2018)
  • Author(s): 大津山 彰
  • Organizer: 日本放射線影響学会 第61回大会