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Myeloid-derived suppressor cells improve corneal graft survival through suppressing angiogenesis and lymphangiogenesis

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机构: [1]Cent South Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha, Hunan, Peoples R China [2]Hunan Clin Res Ctr Ophthalm Dis, Changsha, Hunan, Peoples R China [3]Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
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关键词: LYMPHATIC VESSELS MICE CORNEAL MOUSE MODEL PROTECTION IMMUNITY THERAPY CANCER INOS

摘要:
Myeloid-derived suppressor cells (MDSC) are one of the major negative regulators of immune responses during many pathological conditions such as cancer and transplantation. Emerging evidence indicates that MDSC also contribute to tumor progression through their pro-angiogenic activity in addition to immunosuppressive function. However, virtually nothing is known about the role of MDSC in the regulation of neovascularization after transplantation. Here we showed that antibody-mediated depletion of MDSC in mice led to robust growth of blood and lymphatic neovessels and rapid allograft rejection after corneal penetrating keratoplasty. In contrast, adoptive transfer of ex vivo generated MDSC from cytokine-treated bone marrow cells (evMDSC) suppressed neovascularization and prolonged corneal allograft survival in an inducible nitric oxide synthase (iNOS)-dependent manner. Mechanistically, compared to naive MDSC control, evMDSC have increased expression of an anti-angiogenic factor thrombospondin 1 (Tsp-1) and decreased expression of two critical pro-angiogenic factors, vascular endothelial growth factor A (VEGF-A), and VEGF-C. These findings demonstrate MDSC as a critical anti-angiogenic regulator during transplantation. Our study also indicates that evMDSC are a valuable candidate agent for development of novel cell therapy to improve allograft survival after transplantation.

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基金编号: 81600714 81800855 81500746 81800856 81371054 2017JJ3451 2018JJ3765 2018JJ2576 2017JJ2364 2018zzts927

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出版当年[2020]版:
大类 | 1 区 医学
小类 | 1 区 外科 1 区 移植
最新[2023]版:
大类 | 2 区 医学
小类 | 1 区 移植 2 区 外科
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出版当年[2019]版:
Q1 TRANSPLANTATION Q1 SURGERY
最新[2023]版:
Q1 SURGERY Q1 TRANSPLANTATION

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]Cent South Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha, Hunan, Peoples R China [2]Hunan Clin Res Ctr Ophthalm Dis, Changsha, Hunan, Peoples R China
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通讯机构: [1]Cent South Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha, Hunan, Peoples R China [*1]Cent South Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha, Hunan, Peoples R China [2]Hunan Clin Res Ctr Ophthalm Dis, Changsha, Hunan, Peoples R China [*2]Hunan Clin Res Ctr Ophthalm Dis, Changsha, Hunan, Peoples R China
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