間葉系幹細胞制御による選択的・機能的エキソゾーム誘導

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25461896
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: 田嶋 克史 国立研究開発法人放射線医学総合研究所, 緊急被ばく医療研究センター, プログラムリーダー (80292423)
• Co-Investigator(Kenkyū-buntansha): 羽澤 勝治 金沢大学, 学内共同利用施設等, 助教 (40622460) [Withdrawn] ; 安田 武嗣 国立研究開発法人放射線医学総合研究所, その他部局等, 研究員 (60332269) ; 後藤 孝也 大東文化大学, スポーツ健康科学部, 教授 (80284355) ; 早乙女 愛 国立研究開発法人放射線医学総合研究所, その他部局等, 研究員 (80462688) [Withdrawn]
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 放射線生物学 / 間葉系幹細胞 / 再生医療

Outline of Annual Research Achievements

We investigated effects and molecular mechanisms of mesenchymal stem cells (MSCs) on irradiated cells.
Radiation-induced (8 Gy) human umbilical cord blood cell (HUVECs) death was inhibited by indirectly co-culturing human MSCs in trans-wells, presenting that MSCs may prevent HUVEC death via their producing humoral factors. First, we examined whether exosomes secreted from MSCs have inhibitory effects against radiation-induced cell death. Secreted exosomes clearly demonstrated the protection ability against irradiated cell death.
Next, we examined the basic molecular mechanisms of cellular uptake of exosomes. Radiation increased cellular uptake of exosomes through increasing colocalization of CD29 and CD81 on cellular surfaces. Exosomes became incorporated into cells through selectively binding CD29/CD81 complex on cell surfaces. We also searched affected molecules revealing protection ability against radiation in exosomes. Several factors including anti-apoptotic proteins and micro RNAs, have been detected in exosomes of MSCs. Their functional analyses are under examination.
We found that “a humoral factor A” secreted from MSCs inhibited radiation-induced intestinal epithelial cell death in vitro. Recombinant actor A inhibited radiation-induced epithelial cell death. Its knock-down with siRNA in MSCs lost the protection effects.
Finally, we confirmed that the factor A was effective for intestinal injuries with lower body-irradiated model mouse. These results demonstrated that MSCs and their-derived factors are useful for regeneration of irradiated tissues.

Research Products

• [Journal Article] Characteristics of three-dimensional prospectively isolated mouse bone marrow mesenchymal stem/stromal cell aggregates on nanoculture plates (2016)
  • Author(s): Chizuka Obara, Ken-ichi Tomiyama, Kazuya Takizawa, Rafiqul Islam, Takeshi Yasuda, Takaya Goto, & Katsushi Tajima
  • Journal Title: Cell Tissue Res Volume: 0 Pages: 0
  • DOI: DOI 10.1007/s00441-016-2405-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A prospective analysis of clinical efficacy and safety in chronic myeloid leukemia-chronic phase patients with imatinib resistance or intolerance as evaluated using European Leukemia Net 2013 criteria (2015)
  • Author(s): Murai K, Akagi T, Shimosegawa K, Sugawara T, Ishizawa K, Ito S, Motegi M, Yokoyama H, Noji H, Tajima K, Chou T, Ogawa K, Harigae H, Kubo K, Ooba k, Sakamoto J, Ishida Y
  • Journal Title: Eur J Haematol Volume: 10 Pages: 12536
  • Peer Reviewed / Open Access