The choice of cryopreservation method affects immune compatibility of human cardiovascular matrices.
The choice of cryopreservation method affects immune compatibility of human cardiovascular matrices.
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DOI：
10.1038/s41598-017-17288-z
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发表时间：
2017-12-05
影响因子：
4.6
通讯作者：
Seifert M
中科院分区：
文献类型：
--
作者：
Schneider M;Stamm C;Brockbank KGM;Stock UA;Seifert M
常规冷冻保存（CFC）是目前心血管同种异体移植物保存的金标准。然而，炎症和结构恶化限制了移植的耐久性。无冰冷冻保存（IFC）已经证明了基质结构保存与减弱的免疫反应相结合。在这项研究中，我们的目的是探索这种降低免疫原性的机制在体外。首先，我们的特点因素释放后，CFC和IFC的人主动脉组织。其次，我们分析了与人外周血单核细胞、纯化的单核细胞、T细胞和单核细胞衍生的巨噬细胞的共培养物，以检查由组织或释放的线索触发的功能性免疫效应。IFC组织表现出比CFC组织显著更低的代谢活性和促炎细胞因子的释放，但令人惊讶的是，更活跃的转化生长因子β。由于IFC组织释放的细胞因子减少，在趋化系统中检测到较少的单核细胞和T细胞迁移。此外，只有CFC组织的信号而不是IFC组织的信号扩增的α CD 3触发T细胞增殖。在一个专门设计的巨噬细胞-组织分析中，我们可以表明巨噬细胞在任何一种组织类型上都没有上调M1极化标志物（CD 80或HLA-DR）。总之，IFC选择性地调节组织特性，从而减弱免疫细胞的吸引和激活。因此，IFC治疗为心血管移植物保存创造了更好的机会。
Conventional frozen cryopreservation (CFC) is currently the gold standard for cardiovascular allograft preservation. However, inflammation and structural deterioration limit transplant durability. Ice-free cryopreservation (IFC) already demonstrated matrix structure preservation combined with attenuated immune responses. In this study, we aim to explore the mechanisms of this diminished immunogenicity in vitro. First, we characterized factors released by human aortic tissue after CFC and IFC. Secondly, we analyzed co-cultures with human peripheral blood mononuclear cells, purified monocytes, T cells and monocyte-derived macrophages to examine functional immune effects triggered by the tissue or released cues. IFC tissue exhibited significantly lower metabolic activity and release of pro-inflammatory cytokines than CFC tissue, but surprisingly, more active transforming growth factor β. Due to reduced cytokine release by IFC tissue, less monocyte and T cell migration was detected in a chemotaxis system. Moreover, only cues from CFC tissue but not from IFC tissue amplified αCD3 triggered T cell proliferation. In a specifically designed macrophage-tissue assay, we could show that macrophages did not upregulate M1 polarization markers (CD80 or HLA-DR) on either tissue type. In conclusion, IFC selectively modulates tissue characteristics and thereby attenuates immune cell attraction and activation. Therefore, IFC treatment creates improved opportunities for cardiovascular graft preservation.
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影响因子：
14
作者：
Ariganello, Marianne B.;Simionescu, Dan T.;Labow, Rosalind S.;Lee, J. Michael
通讯作者：
Lee, J. Michael
心脏瓣膜组织的玻璃化。
DOI：
10.1007/978-1-4939-2193-5_20
发表时间：
2015
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Brockbank KG;Chen Z;Greene ED;Campbell LH
通讯作者：
Campbell LH
影响因子：
1.5
作者：
Jadlowiec, Caroline C.;Lavallee, Matthew;Brown, Matthew G.
通讯作者：
Brown, Matthew G.
影响因子：
46.9
作者：
Giwa S;Lewis JK;Alvarez L;Langer R;Roth AE;Church GM;Markmann JF;Sachs DH;Chandraker A;Wertheim JA;Rothblatt M;Boyden ES;Eidbo E;Lee WPA;Pomahac B;Brandacher G;Weinstock DM;Elliott G;Nelson D;Acker JP;Uygun K;Schmalz B;Weegman BP;Tocchio A;Fahy GM;Storey KB;Rubinsky B;Bischof J;Elliott JAW;Woodruff TK;Morris GJ;Demirci U;Brockbank KGM;Woods EJ;Ben RN;Baust JG;Gao D;Fuller B;Rabin Y;Kravitz DC;Taylor MJ;Toner M
通讯作者：
Toner M
影响因子：
4.6
作者：
Brown, John W.;Ruzmetov, Mark;Turrentine, Mark W.
通讯作者：
Turrentine, Mark W.