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- Material Type
- 文書・図像類
- Author/Editor
- 佐原, 寿史
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- Alternative Title
- Establishment of a new strategy to improve graft function after lung transplantation from brain-dead using mesenchymal stem cells : preclinical study using MHC-inbred CLAWN miniature swine
- Text Language Code
- jpn
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- Target Audience
- 一般
- Note (General)
- 2012-2013年度科学研究費助成事業（挑戦的萌芽研究）研究成果報告書 課題番号：24659637 研究代表者：佐原寿史（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）脳死状態では、不安定な循環・代謝状態、炎症の活性化など様々な変化が起こる。ドナー拡大及び移植成績の更なる向上を目指すドナー臓器保護戦略として、障害部位に集積する走化性をもち、局所の炎症や免疫反応を抑制作用をもつ間葉系幹細胞（mesenchymal stem cell: MSC）に着目し、脳死ドナーへのMSC投与効果を評価する前臨床研究を開始した。その結果、ミニブタ脳死肺移植モデルの確立と特徴を評価し（脳死肺内での炎症亢進とそれに伴う拒絶反応促進）、2） ミニブタMSCの樹立（脂肪・骨髄組織）をはかり、MSCのドナー投与による移植肺虚血再灌流障害抑制と生着延長効果の評価へとつながる結果を得た。Physiologic changes at brain death (BD) would affect the organ suitability and out come 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.