Effect of mesenchymal stem cells on septic acute renal failure

• Project/Area Number: 24592756
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Fujita Health University
• Principal Investigator: TAKEYAMA Naoshi 藤田保健衛生大学, 医学部, 教授 (00155053)
• Co-Investigator(Kenkyū-buntansha): HIRAKAWA Akihiko 藤田保健衛生大学, 医学部, 教授 (00319633) ; TSUDA Masanobu 藤田保健衛生大学, 医学部, 准教授 (70506683)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 敗血症 / T細胞 / 遺伝子解析 / PD-１ / multiplex PCR / 血管内皮前駆細胞 / angiopoietin 1 / CXCL8 / cf-DNA / DAMPs

Outline of Final Research Achievements

We investigated the impact of sepsis on the adaptive immune system and to monitor T cell receptor (TCR) diversity. TCR diversity was markedly decreased in septic patients at day 1 compared to the healthy volunteer. A recovery of TCR diversity was observed at days 3 and 7 except for dead patient. HLA-DR expression was significantly decreased in septic patients at day 1. Total lymphocyte count reduced in septic patients at day 1, but lymphocyte count recovered at days 3 and 7 except for dead patient. We observed a lower TCR diversity and lymphopenia in early stage of septic shock. A quickly recovery of TCR diversity and lymphocyte count were observed in live patients. On the other hand, dead patient stayed on the lower level over the course of the study. These results suggest that altered TCR diversity and lymphopenia might participate in increased mortality and susceptibility to secondary nosocomial infections.

Research Products

• [Journal Article] Neutrophil extracellular traps in patients with sepsis. (2015)
  • Author(s): Hashiba M, Huq MA, Tomino A, Hirakawa A, Hattori T, Miyabe H, Tsuda M, and Takeyama N
  • Journal Title: J Surg Res Volume: 194 Pages: 248-254
  • Peer Reviewed
• [Journal Article] Successful treatment of septic shock due to New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae in a patient transferred from India to Japan. (2014)
  • Author(s): Kano H, Hirakawa A, Miyabe H, Hattori T, Mikamo H, Yoshida S, and Takeyama N
  • Journal Title: Acute Medicine & Surgery Volume: 1 Pages: 181-185
  • Peer Reviewed
• [Journal Article] 敗血症性ショック患者におけるT細胞機能障害 (2014)
  • Author(s): 武山直志、富野敦稔、波柴尉充、安藤雅規、後長孝佳、宮部浩道、津田雅庸、服部友紀、加納秀記、平川昭彦
  • Journal Title: 日本ショック学会誌 Volume: 29 Pages: 9-12
  • Peer Reviewed
• [Presentation] INCREASED PD-1 EXPRESSION AND ALTERED T CELL REPERTOIRE DIVERSITY IN SEPTIC SHOCK PATIENTS (2015)
  • Author(s): N. Takeyama, A. Tomino, M. Hashiba, M. Ando, T. Gocho, H. Miyabe, H. Kano, M. Tsuda, T. Hattori, A. Hirakawa
  • Organizer: 38th Shock Society Annual Conference
  • Place of Presentation: Denver
  • Year and Date: 2015-06-04 – 2015-06-09
  • Invited
• [Presentation] Ex vivo and in vivo generation of neutrophil extracellular traps by neutrophils from septic patients. (2015)
  • Author(s): Takeyama N, Huq MA, Ando M, Gocho T, Tomino A, Miyabe H, Kano H, Tsuda M, Hattori T, Hirakawa A, Hashiba M.
  • Organizer: 35th International symposium on Intensive Care and Emergency medicine
  • Place of Presentation: Brussels
  • Year and Date: 2015-03-17 – 2015-03-20
• [Presentation] Altered T cell repertoire diversity in septic shock patients (2014)
  • Author(s): Takeyama N, Tomino A, Hashiba M, Hirakawa A, Hattori T, Miyabe H
  • Organizer: 31st International symposium on Intensive Care and Emergency medicine
  • Place of Presentation: Brussels