Investigation of the effects of autologous bone marrow and spleen cells on pulmonary fibrosis

• Project/Area Number: 26461201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Nippon Medical School
• Principal Investigator: Kamio Koichiro 日本医科大学, 医学部, 助教 (20465305)
• Co-Investigator(Kenkyū-buntansha): 吾妻 安良太 日本医科大学, 医学部, 教授 (10184194)
• Research Collaborator: MATSUDA Kuniko 日本医科大学, 実験助手
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 制御性T細胞 / 特発性肺線維症 / ブレオマイシン / FGF9 / IL-10 / 自家骨髄細胞 / 再生医療

Outline of Final Research Achievements

In the current study, we aimed at the resolution of pulmonary fibrosis using autologous bone marrow or spleen cells. Pulmonary fibrosis was induced by bleomycin (BLM) (day 0), then, bone marrow cells or spleen cells were adoptively transferred via tail veins on day 7 or 14.
Adoptive transfer of spleen cells significantly ameliorated BLM-induced murine pulmonary fibrosis on day14. This effect was abrogated by neutralization of CD25 by anti-CD25 monoclonal antibody, which suggests that regulatory T cells (Tregs) are involved in the effect of spleen cells.
To further characterize the mechanisms by which Tregs exert anti-fibrotic effects, we isolated Tregs from spleens of C57BL/6 mice using magnetic beads, then, adoptively transferred them into BLM-induced pulmonary fibrosis mice on day 14. Tregs significantly ameliorated pulmonary fibrosis which was measured by Ashcroft score and hydroxyproline. This was accompanied by reduced expression of fibroblast growth factor 9 and IL-10.

Research Products

• [Journal Article] XPLN is modulated by HDAC inhibitors and negatively regulates SPARC expression by targeting mTORC2 in human lung fibroblasts (2017)
  • Author(s): Koichiro Kamio, Arata Azuma, Jiro Usuki, Kuniko Matsuda, Minoru Inomata, Nobuhiko Nishijima, Shioto Itakura, Hiroki Hayashi, Takeru Kashiwada, Nariaki Kokuho, Kenichiro Atsumi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
  • Journal Title: Pulmonary Pharmacology & Therapeutics Volume: 44 Pages: 61-69
  • DOI: 10.1016/j.pupt.2017.03.003
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] XPLN Negatively Regulates SPARC Expression by Targeting mTORC2 in Human Lung Fibroblasts (2016)
  • Author(s): Koichiro Kamio, Arata Azuma, Jiro Usuki, Kuniko Matsuda, Minoru Inomata, Nobuhiko Nishijima, Shioto Itakura, Nariaki Kokuho, Hiroki Hayashi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
  • Organizer: American Thoracic Society
  • Place of Presentation: 米国サンフランシスコ
  • Year and Date: 2016-05-14
  • Int'l Joint Research