Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction
Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction
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DOI：
10.1161/01.cir.0000134696.08436.65
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发表时间：
2004-06-29
期刊：
影响因子：
37.8
通讯作者：
Losordo, DW
中科院分区：
文献类型：
--
作者：
Yoon, YS;Park, JS;Losordo, DW
背景-使用骨髓（BM）细胞或BM细胞的单核部分治疗缺血性心脏病的临床试验数量迅速增加。方法和结果7周龄雌性Fisher-344大鼠接受手术诱导急性心肌梗死，并随机分为3组，每组16只大鼠，每组接受心肌内注射7 × 10（5）DiI标记的总BM细胞（TBMCs），在梗死周围区域中，使用相同数量的DiI标记的克隆扩增的BM多能干细胞，或相同体积的磷酸盐缓冲盐水。细胞移植后2周超声心动图显示TBMC组14只存活大鼠中有4只（28.5%）心肌内钙化。苏木精-伊红染色和von Kossa染色的组织学检查证实存在广泛的心肌内钙化。碱性磷酸酶染色显示钙化区域周围呈强阳性，提示正在进行的成骨活性。荧光显微镜检查显示，脱细胞钙化区周围的二碘标记的TBMCs，表明移植的TBMCs直接参与心肌钙化。相比之下，在心脏接受等量的生理盐水或BM多能干细胞以同样的方式交付，有没有证据calcium. Conclusions这些结果表明，直接移植到急性心肌梗死的BM细胞可能会引起显着的心肌内钙化。
Background-There has been a rapid increase in the number of clinical trials using unselected bone marrow ( BM) cells or the mononuclear fraction of BM cells for treating ischemic heart diseases. Thus far, no significant deleterious effects or complications have been reported in any studies using BM-derived cells for treatment of various cardiac diseases.Methods and Results-Seven-week-old female Fisher-344 rats underwent surgery to induce acute myocardial infarction and were randomized into 3 groups of 16 rats, each receiving intramyocardial injection of either 7 x 10(5) DiI-labeled total BM cells (TBMCs), the same number of DiI-labeled, clonally expanded BM multipotent stem cells, or the same volume of phosphate-buffered saline in the peri-infarct area. Echocardiography 2 weeks after cell transplantation indicated intramyocardial calcification in 4 of 14 surviving rats (28.5%) in the TBMC group. Histological examination with hematoxylin and eosin staining and von Kossa staining confirmed the presence of extensive intramyocardial calcification. Alkaline phosphatase staining revealed strong positivity surrounding the calcified area suggestive of ongoing osteogenic activity. Fluorescent microscopic examination revealed that acellular calcific areas were surrounded by DiI-labeled TBMCs, suggesting the direct involvement of transplanted TBMCs in myocardial calcification. In contrast, in hearts receiving equal volumes of saline or BM multipotent stem cells delivered in the same manner, there was no evidence of calcification.Conclusions-These results demonstrate that direct transplantation of unselected BM cells into the acutely infarcted myocardium may induce significant intramyocardial calcification.