Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia.
Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia.
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DOI：
10.46582/jsrm.0803010
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发表时间：
2012
影响因子：
2.7
通讯作者：
Umezawa A
中科院分区：
文献类型：
--
作者：
Kimura M;Toyoda M;Gojo S;Itakura Y;Kami D;Miyoshi S;Kyo S;Ono M;Umezawa A
导论.羊膜含有多能干细胞群，并被认为具有调节免疫反应的机制。我们研究了同种异体羊膜间充质基质细胞（AMSC）移植在猪慢性心肌缺血模型中的安全性和有效性，作为临床前试验。方法.从分娩前通过剖宫产获得的羊膜中分离猪AMSC，并在移植前培养以增加其数量。在冠状动脉左回旋支周围植入Ameroid缩窄器诱导慢性心肌缺血。缺血诱导4周后，9只猪被分配接受异基因AMSC移植或注射生理盐水。移植后4周行超声心动图功能分析，免疫组化组织学检查。结果超声心动图显示AMSC移植后4周左室射血分数明显改善，左室扩张明显减轻。组织学评估显示AMSC移植组的纤维化百分比显著降低。移植后4周，在免疫活性宿主心脏中鉴定了注射的同种异体表达绿色荧光蛋白（GFP）的AMSC，未使用任何免疫抑制剂。免疫组化显示GFP与心肌肌钙蛋白T和心肌肌钙蛋白I共定位。结论.我们已经证明，同种异体AMSC移植在慢性心肌缺血的猪模型中受损的心肌中产生组织学和功能改善。移植的同种异体AMSC在不使用任何免疫抑制剂的情况下存活，并通过其转分化或细胞融合获得心脏表型。
Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC) transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP)-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.