Clinical Cellular Therapeutics Accelerate Clot Formation.
Clinical Cellular Therapeutics Accelerate Clot Formation.
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DOI：
10.1002/sctm.18-0015
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发表时间：
2018-10
影响因子：
6
通讯作者：
Cox CS Jr
中科院分区：
文献类型：
--
作者：
George MJ;Prabhakara K;Toledano-Furman NE;Wang YW;Gill BS;Wade CE;Olson SD;Cox CS Jr
临床细胞疗法（CCTs）在减轻创伤后炎症、保持心肌梗死后心功能和改善脑卒中后功能恢复方面已显示出初步疗效。然而，大多数临床可用的细胞系表达刺激凝血的组织因子（TF）。我们试图确定cct的促凝活性程度与TF表达的关系。对骨髓、脂肪、羊水、脐带、多能成人祖细胞供体和骨髓单核细胞的CCT样本进行了测试。流式细胞术定量检测TF表达和表型。CCTs的促凝活性在体外通过血栓弹性成像和校准血栓图进行测量。荧光活化细胞分选（FACS）将样品分为高表达和低表达TF的群体，以分离TF对凝血的贡献。将TF中和抗体与样品一起孵育，以证明其促凝功能的丧失。所有cct均表达促凝活性与组织因子表达相关。随着TF表达的增加，凝血时间和凝血酶形成时间缩短。当使用流式细胞术从单个供体中分离出高表达TF的细胞时，其凝血时间比低表达TF的细胞缩短。一种TF中和抗体使部分（但不是全部）CCT样品的凝血时间恢复到控制值。CCTs显示与TF表达相关的促凝活性具有广泛的可变性。凝血时间和凝血酶的形成随着TF负荷的增加而减少，这种促凝作用被TF阻断抗体所中和。使用cct的临床试验正在进行中，TF表达可能成为一种安全释放标准。干细胞转化医学2018；7:731 - 739
Clinical cellular therapeutics (CCTs) have shown preliminary efficacy in reducing inflammation after trauma, preserving cardiac function after myocardial infarction, and improving functional recovery after stroke. However, most clinically available cell lines express tissue factor (TF) which stimulates coagulation. We sought to define the degree of procoagulant activity of CCTs as related to TF expression. CCT samples from bone marrow, adipose, amniotic fluid, umbilical cord, multi‐potent adult progenitor cell donors, and bone marrow mononuclear cells were tested. TF expression and phenotype were quantified using flow cytometry. Procoagulant activity of the CCTs was measured in vitro with thromboelastography and calibrated thrombogram. Fluorescence‐activated cell sorting (FACS) separated samples into high‐ and low‐TF expressing populations to isolate the contribution of TF to coagulation. A TF neutralizing antibody was incubated with samples to demonstrate loss of procoagulant function. All CCTs tested expressed procoagulant activity that correlated with expression of tissue factor. Time to clot and thrombin formation decreased with increasing TF expression. High‐TF expressing cells decreased clotting time more than low‐TF expressing cells when isolated from a single donor using FACS. A TF neutralizing antibody restored clotting time to control values in some, but not all, CCT samples. CCTs demonstrate wide variability in procoagulant activity related to TF expression. Time to clot and thrombin formation decreases as TF load increases and this procoagulant effect is neutralized by a TF blocking antibody. Clinical trials using CCTs are in progress and TF expression may emerge as a safety release criterion. Stem Cells Translational Medicine 2018;7:731–739
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影响因子：
12.4
作者：
Liao L;Shi B;Chang H;Su X;Zhang L;Bi C;Shuai Y;Du X;Deng Z;Jin Y
通讯作者：
Jin Y
DOI：
10.1016/j.bbrc.2013.05.013
发表时间：
2013-06-14
影响因子：
3.1
作者：
Hogan, Niamh M.;Joyce, Myles R.;Dwyer, Roisin M.
通讯作者：
Dwyer, Roisin M.
影响因子：
3.7
作者：
Pati S;Gerber MH;Menge TD;Wataha KA;Zhao Y;Baumgartner JA;Zhao J;Letourneau PA;Huby MP;Baer LA;Salsbury JR;Kozar RA;Wade CE;Walker PA;Dash PK;Cox CS Jr;Doursout MF;Holcomb JB
通讯作者：
Holcomb JB
DOI：
10.1097/ta.0b013e3181a51e33
发表时间：
2009-06-01
影响因子：
--
作者：
Van, Philbert Y.;Cho, S. David;Schreiber, Martin A.
通讯作者：
Schreiber, Martin A.
影响因子：
15.1
作者：
Hincker, Alexander;Feit, Justin;Wagener, Gebhard
通讯作者：
Wagener, Gebhard