Therapeutic angiogenesis with preconditioned stem cells for clinical settings

Research Project

Project/Area Number	25462162
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Cardiovascular surgery
Research Institution	Yamaguchi University
Principal Investigator	KATSURA Shunsaku 山口大学, 医学部附属病院, 助教 (40457304)
Co-Investigator(Kenkyū-buntansha)	HAMANO Kimikazu 山口大学, 大学院医学系研究科, 教授 (60263787) HOSOYAMA Tohru 山口大学, 大学院医学系研究科, 助教 (20638803) LI Tao-sheng 長崎大学, 原爆後障害医療研究所, 教授 (50379997)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	細胞移植治療 / 末梢血単核球 / 低酸素プレコンディショニング / 前臨床試験 / 重症下肢虚血
Outline of Final Research Achievements	Peripheral blood mononuclear cell (PBMNC) is one of powerful tools for therapeutic angiogenesis in hindlimb ischemia. However, traditional approaches with transplanted PBMNCs show poor therapeutic effects in severe ischemia patients. In this study, we used autograft models to determine whether hypoxic pretreatment effectively enhances the cellular functions of PBMNCs and improves hindlimb ischemia. Preconditioned rabbit PBMNCs showed significantly enhanced functional capacities in resistance to oxidative stress, and cell viability. In addition, autologous transplantation of preconditioned rabbit PBMNCs significantly induced new vessels and improved limb blood flow. Our study demonstrated that hypoxic preconditioning of PBMNCs is a feasible approach for increasing the retention of transplanted cells and enhancing therapeutic angiogenesis in ischemic tissue.