Mesenchymal cell transplantation and myocardial remodeling after myocardial infarction.
Mesenchymal cell transplantation and myocardial remodeling after myocardial infarction.
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DOI：
10.1161/circulationaha.108.842302
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发表时间：
2009-09-15
期刊：
影响因子：
37.8
通讯作者：
Spinale FG
中科院分区：
文献类型：
--
作者：
Dixon JA;Gorman RC;Stroud RE;Bouges S;Hirotsugu H;Gorman JH 3rd;Martens TP;Itescu S;Schuster MD;Plappert T;St John-Sutton MG;Spinale FG
间充质前体细胞（MPCs）的靶向递送可以改变心肌梗死（MI）后左心室（LV）细胞和细胞外重塑。然而，心肌梗死后注射MPC是否以及在何种程度上影响LV重塑，以及这些影响是否具有浓度依赖性仍然未知。从绵羊骨髓中扩增同种异体MPCs，并在MI诱导后1小时在边缘区进行直接心肌内注射（冠状动脉结扎）在绵羊中的浓度如下：25×106（25 M，n=7）、75 ×106（75 M，n=7）、225 ×106（225 M，n=10）、450 ×106（450 M，n=8）和仅无MPC培养基（仅MI，n=14）。所有组的LV舒张末期容积均增加，但25和75 M组的LV舒张末期容积减小。仅MI组、225 M组和450 M组中，边界区域内的胶原蛋白含量增加。而血浆ICTP（胶原降解指数）在25 M组中最高。在边界区，基质金属蛋白酶（MMPs）和MMP组织抑制剂（TIMPs）也以MPC浓度依赖性方式变化。例如，与仅MI和其他MPC治疗组值相比，25 M组中MMP-9的边界区水平最高。MPC注射以浓度依赖性方式改变胶原动力学、MMP和TIMP水平，从而影响MI后LV重构指数。然而，在较低的MPC浓度下确定了关于MI后重塑的最大效果，从而表明对于这种特定的细胞疗法存在治疗阈值。
Targeted delivery of mesenchymal precursor cells (MPCs) can modify left ventricular (LV) cellular and extracellular remodeling following myocardial infarction (MI). However, whether and to what degree LV remodeling may be affected by MPC injection post-MI, and whether these effects are concentration dependent remain unknown. Allogeneic MPCs were expanded from sheep bone marrow, and direct intra-myocardial injection was performed within the borderzone region one hour following MI induction (coronary ligation) in sheep at the following concentrations: 25×106 (25 M, n=7), 75 ×106 (75 M, n=7), 225 ×106 (225 M, n=10), 450 ×106 (450 M, n=8), and MPC free media only (MI Only, n=14). LV end diastolic volume increased in all groups but was attenuated in the 25 and 75 M groups. Collagen content within the borderzone region was increased in the MI Only, 225, and 450 M groups. Whereas plasma ICTP, an index of collagen degradation, was highest in the 25 M group. Within the borderzone region matrix metalloproteinases (MMPs) and MMP tissue inhibitors (TIMPs) also changed in a MPC concentration dependent manner. For example, borderzone levels of MMP-9 were highest in the 25 M group when compared to the MI Only and other MPC treatment group values. MPC injection altered collagen dynamics, MMP, and TIMP levels in a concentration dependent manner, and thereby influenced indices of post-MI LV remodeling. However, the greatest effects with respect to post-MI remodeling were identified at lower MPC concentrations, thus suggesting a therapeutic threshold exists for this particular cell therapy.