Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage.
Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage.
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DOI：
10.1016/j.athoracsur.2008.11.057
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发表时间：
2009-03
影响因子：
4.6
通讯作者：
Gorman, Robert C.
中科院分区：
文献类型：
--
作者：
Hamamoto, Hirotsugu;Gorman, Joseph H., III;Ryan, Liam P.;Hinmon, Robin;Martens, Timothy P.;Schuster, Michael D.;Plappert, Theodore;Kiupel, Matti;John-Sutton, Martin G. St.;Itescu, Silviu;Gorman, Robert C.
该实验评估了独特的同种异体 STRO-3 阳性间充质前体细胞 (MPC) 对梗死后左心室 (LV) 重塑的剂量依赖性影响。 MPC 的给药方式模拟绵羊透壁心肌梗塞 (MI) 模型中心肌细胞治疗的自然、梗塞后早期预防性方法。同种异体 MPC 是从雄性杂交羊中分离出来的。 46 只雌性绵羊接受冠状动脉结扎术以产生透壁性左心室前心尖梗塞。梗死后一小时，边界区心肌注射 25、75、225 或 450 × 106 MPC 或细胞培养基。 MI 后 4 周和 8 周进行超声心动图，以量化左心室舒张末期 (LVEDV) 和收缩末期容积 (LVESV)、射血分数 (EF) 和梗塞扩张。对梗塞和边缘区标本进行 CD31 和平滑肌肌动蛋白 (SMA) 免疫组织化学染色，以量化血管密度。与对照组相比，低剂量（25 和 75 × 106 细胞）MPC 治疗显着减弱了梗塞扩张以及 LVEDV 和 LVESV 的增加。所有细胞剂量下的 EF 均得到改善。 CD31 和 SMA 免疫组织化学染色表明，仅在较低的细胞剂量下，边界区的血管密度才会增加。梗塞内没有心肌再生的证据。在临床相关的大型动物模型中，同种异体 STRO-3 阳性 MPC 减弱了对透壁 MI 的重塑反应。这种效应与边界区和梗塞内的血管生成和动脉生成有关，并且在较低的细胞剂量下最为明显。
This experiment assessed the dose-dependent effect of a unique allogeneic STRO-3–positive mesenchymal precursor cell (MPC) on postinfarction left ventricular (LV) remodeling. The MPCs were administered in a manner that would simulate an off-the-self, early postinfarction, preventative approach to cardiac cell therapy in a sheep transmural myocardial infarct (MI) model. Allogeneic MPCs were isolated from male crossbred sheep. Forty-six female sheep underwent coronary ligation to produce a transmural LV anteroapical infarction. One hour after infarction, the borderzone myocardium received an injection of 25, 75, 225, or 450 × 106 MPCs, or cell medium. Echocardiography was performed at 4 and 8 weeks after MI to quantify LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), ejection fraction (EF), and infarct expansion. CD31 and smooth muscle actin (SMA) immunohistochemical staining was performed on infarct and borderzone specimens to quantify vascular density. Compared with controls, low-dose (25 and 75 × 106 cells) MPC treatment significantly attenuated infarct expansion and increases in LVEDV and LVESV. EF was improved at all cell doses. CD31 and SMA immunohistochemical staining demonstrated increased vascular density in the borderzone only at the lower cell doses. There was no evidence of myocardial regeneration within the infarct. Allogeneic STRO-3 positive MPCs attenuate the remodeling response to transmural MI in a clinically relevant large-animal model. This effect is associated with vasculogenesis and arteriogenesis within the borderzone and infarct and is most pronounced at lower cell doses.
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影响因子：
4.6
作者：
MARKOVITZ, LJ;SAVAGE, EB;EDMUNDS, LH
通讯作者：
EDMUNDS, LH
影响因子：
82.9
作者：
Kocher, AA;Schuster, MD;Itescu, S
通讯作者：
Itescu, S
影响因子：
4.6
作者：
Narula, N;Narula, J;Tomaszewski, JE
通讯作者：
Tomaszewski, JE
DOI：
10.1152/ajpheart.00058.2004
发表时间：
2004-08-01
影响因子：
4.8
作者：
Schuster, MD;Kocher, AA;Itescu, S
通讯作者：
Itescu, S
影响因子：
158.5
作者：
Schaechinger, Volker;Erbs, Sandra;Zeiher, Andreas M.
通讯作者：
Zeiher, Andreas M.