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植入Carmat生物人工全心脏一个月后观察到循环干细胞水平升高。

Elevated Circulating Stem Cells Level is Observed One Month After Implantation of Carmat Bioprosthetic Total Artificial Heart.

作者信息

Guyonnet Léa, Detriché Grégoire, Gendron Nicolas, Philippe Aurélien, Latremouille Christian, Soret Lou, Capel Antoine, Peronino Christophe, Jansen Piet, Ivak Peter, Carpentier Alain, Mirault Tristan, Netuka Ivan, Guerin Coralie L, Smadja David M

机构信息

Institut Curie, Cytometry Platform, 75006, Paris, France.

Innovative Therapies in Haemostasis, INSERM, Université de Paris, 75006, Paris, France.

出版信息

Stem Cell Rev Rep. 2021 Dec;17(6):2332-2337. doi: 10.1007/s12015-021-10270-3. Epub 2021 Oct 7.

Abstract

The Aeson® total artificial heart (A-TAH) has been developed as a total heart replacement for patients at risk of death from biventricular failure. We previously described endothelialization of the hybrid membrane inside A-TAH probably at the origin of acquired hemocompatibility. We aimed to quantify vasculogenic stem cells in peripheral blood of patients with long-term A-TAH implantation. Four male adult patients were included in this study. Peripheral blood mononuclear cells were collected before A-TAH implantation (T0) and after implantation at one month (T1), between two and five months (T2), and then between six and twelve months (T3). Supervised analysis of flow cytometry data confirmed the presence of the previously identified LinCD133CD45 and LinCD34 with different CD45 level intensities. LinCD133CD45, LinCD34CD45 and LinCD34CD45 were not modulated after A-TAH implantation. However, we demonstrated a significant mobilization of LinCD34CD45 (p = 0.01) one month after A-TAH implantation regardless of the expression of CD133 or c-Kit. We then visualized data for the resulting clusters on a uniform manifold approximation and projection (UMAP) plot showing all single cells of the live Lin and CD34 events selected from down sampled files concatenated at T0 and T1. The three clusters upregulated at T1 are CD45 clusters, confirming our results. In conclusion, using a flow cytometry approach, we demonstrated in A-TAH-transplanted patients a significant mobilization of LinCD34CD45 in peripheral blood one month after A-TAH implantation. Using a flow cytometry approach, we demonstrated in A-TAH transplanted patients a significant mobilization of LinCD34CD45 in peripheral blood one month after A-TAH implantation. This cell population could be at the origin of newly formed endothelial cells on top of hybrid membrane in Carmat bioprosthetic total artificial heart.

摘要

Aeson®全人工心脏(A-TAH)已被开发用于替代有因双心室衰竭而死亡风险的患者的整个心脏。我们之前描述了A-TAH内部混合膜的内皮化,这可能是获得性血液相容性的起源。我们旨在量化长期植入A-TAH的患者外周血中的血管生成干细胞。本研究纳入了4名成年男性患者。在植入A-TAH之前(T0)以及植入后1个月(T1)、2至5个月(T2)、6至12个月(T3)采集外周血单个核细胞。流式细胞术数据的监督分析证实了先前鉴定出的具有不同CD45水平强度的LinCD133CD45和LinCD34的存在。A-TAH植入后,LinCD133CD45、LinCD34CD45和LinCD34CD45未发生调节。然而,我们证明了A-TAH植入后1个月,无论CD133或c-Kit的表达如何,LinCD34CD45均有显著动员(p = 0.01)。然后,我们在统一流形近似和投影(UMAP)图上可视化了所得聚类的数据,该图显示了从T0和T1连接的下采样文件中选择的活Lin和CD34事件的所有单细胞。在T1上调的三个聚类是CD45聚类,证实了我们的结果。总之,使用流式细胞术方法,我们在接受A-TAH移植的患者中证明,A-TAH植入后1个月外周血中LinCD34CD45有显著动员。使用流式细胞术方法,我们在接受A-TAH移植的患者中证明,A-TAH植入后1个月外周血中LinCD34CD45有显著动员。该细胞群体可能是Carmat生物假体全人工心脏中混合膜上新形成的内皮细胞的起源。

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