Establishment of a new strategy to improve graft function after lung transplantation from brain-dead donors using mesenchymal stem cells - preclinical study using MHC-inbred CLAWN miniature swine

• Project/Area Number: 24659637
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Thoracic surgery
• Research Institution: Kagoshima University
• Principal Investigator: SAHARA Hisashi 鹿児島大学, 医用ミニブタ・先端医療開発研究センター, 准教授 (90452333)
• Co-Investigator(Kenkyū-buntansha): YAMADA Kazuhiko 鹿児島大学, 医用ミニブタ・先端医療開発 研究センター, 教授 (40241103)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 移植・再生医療 / トランスレーショナルリサーチ / 肺移植 / 間葉系幹細胞 / 脳死 / 臓器保護 / ミニブタ / 脳死ドナー

Research Abstract

Physiologic changes at brain death (BD) would affect the organ suitability and outcome of transplantation. We first examined whether donor BD affects early lung function and graft survival using MHC-defined CLAWN miniature swine. Up-regulation of proinflammatory cytokines as early as 6h after BD induction was observed in the BD donor associated with inflammatory cell infiltrates on 2-hour and 2-day biopsies. Moreover, graft survival using BD donor was significantly shorter compared to the non-BD donor (26 days vs 47 days). Next to establish a new strategy to reduce inflammatory change after brain death, we tried to establish porcine mesenchymal stem cells (MSC) derived from bone marrow and adipose tissue, and successfully cultured them. After confirmation of the characteristics of these cells as MSC, we evaluate whether injection of MSC to brain-dead donor contribute to improve graft function and survival using preclinical lung transplant model of miniature swine.

Research Products

• [Presentation] シンポジウム2「各系統実験用ブタ紹介」MHC確立クラウン系ミニブタを用いた同種移植実験 (2013)
  • Author(s): 佐原寿史、岩永健裕、山田和彦
  • Organizer: 第1回日本先進医工学ブタ研究会
  • Place of Presentation: 大阪市
  • Year and Date: 2013-11-12
• [Presentation] Beneficial effects of inhaled carbon monoxide (CO) to brain-dead (BD) donors on prolonging pulmonary allograft survival in MHC-inbred CLAWN miniature swine (2013)
  • Author(s): Miura K, Sahara H, Waki S, Kawai A, Shimizu A, Yamada K
  • Organizer: The 13th Congress of the Asian Society of Transplantation
  • Place of Presentation: Kyoto, Japan
• [Presentation] Carbon monoxide (CO) inhalation prolongs survival of the fully MHC-disparate lung graft from brain death donors in miniature swine (2013)
  • Author(s): Sahara H, Miura K, Kawai A, Waki S, Sekijima M, Shimizu A, Yamada K
  • Organizer: International Society for Heart and Lung Transplantation 33rd Annual Meeting
  • Place of Presentation: Montreal, Canada
• [Presentation] シンポジウム2「各系統実験用ブタ紹介」MHC確立クラウン系ミニブタを用いた同種移植実験 (2013)
  • Author(s): 佐原寿史
  • Organizer: 第1回日本先進医工学ブタ研究会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] Carbon monoxide (CO) inhalation prolongs survival of the fully MHC-disparate lung graft from brain death donors in miniature swine (2013)
  • Author(s): Sahara H, Miura K, Kawai A, Waki S, Sekijima M, Shimizu A, Yamada K
  • Organizer: International Society for Heart and Lung Transplantation 33rd Annual Meeting
  • Place of Presentation: モントリオール
• [Remarks]
  • URL: http://www.kufm.kagoshima-u.ac.jp/~xenotx/
• [Remarks] 医用ミニブタ・先端医療開発研究センターホームページ
  • URL: http://www.kufm.kagoshima-u.ac.jp/~xenotx/