Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart
Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart
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DOI：
10.1161/circulationaha.107.732073
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发表时间：
2008-03-25
期刊：
影响因子：
37.8
通讯作者：
Abraham, M. Roselle
中科院分区：
文献类型：
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作者：
Terrovitis, John;Stuber, Matthias;Abraham, M. Roselle
用氧化铁颗粒标记干细胞可以通过磁共振成像（MRI）检测标记的细胞，通常用于跟踪干细胞植入。然而，MRI用于区分存活的ferumoxide标记细胞与其他MRI信号来源（例如，含有从非存活细胞释放的ferumoxide的巨噬细胞）的有效性尚未得到彻底研究。我们试图确定注射同系或异种铁氧化物标记干细胞后3周铁依赖性MRI信号的持续性与细胞存活之间的关系方法和结果-我们研究了非免疫豁免的人类和大鼠心脏来源的干细胞和人类间充质干细胞，这些细胞用铁氧化物和β-半乳糖苷酶双重标记，并将其心肌内注射到免疫活性的Wistar大鼠中。京都的老鼠。在干细胞注射后2天和3周，在临床3-T MRI扫描仪中对动物进行成像。在第2天，通过MRI将异种和同系细胞（心脏源性干细胞和间充质干细胞）的注射部位鉴定为持续3周的大的心肌内信号空隙（初始信号的50%至90%）。组织学（在3周时）显示在注射部位存在含铁巨噬细胞，通过CD 68染色鉴定，但在移植有同基因或异种细胞的动物中很少或没有β-半乳糖苷酶阳性干细胞，结论-铁氧化物引起的显著的铁依赖性MRI信号的持续性-含有巨噬细胞，尽管移植后3周很少或没有活的干细胞，表明阿魏酸标记的细胞的MRI不能可靠地报告心脏中的长期干细胞植入。
Background - Stem cell labeling with iron oxide ( ferumoxide) particles allows labeled cells to be detected by magnetic resonance imaging ( MRI) and is commonly used to track stem cell engraftment. However, the validity of MRI for distinguishing surviving ferumoxide-labeled cells from other sources of MRI signal, for example, macrophages containing ferumoxides released from nonsurviving cells, has not been thoroughly investigated. We sought to determine the relationship between the persistence of iron-dependent MRI signals and cell survival 3 weeks after injection of syngeneic or xenogeneic ferumoxides-labeled stem cells (cardiac-derived stem cells) in rats.Methods and Results - We studied nonimmunoprivileged human and rat cardiac-derived stem cells and human mesenchymal stem cells doubly labeled with ferumoxides and beta-galactosidase and injected intramyocardially into immunocompetent Wistar-Kyoto rats. Animals were imaged at 2 days and 3 weeks after stem cell injection in a clinical 3-T MRI scanner. At 2 days, injection sites of xenogeneic and syngeneic cells (cardiac-derived stem cells and mesenchymal stem cells) were identified by MRI as large intramyocardial signal voids that persisted at 3 weeks (50% to 90% of initial signal). Histology ( at 3 weeks) revealed the presence of iron-containing macrophages at the injection site, identified by CD68 staining, but very few or no beta-galactosidase - positive stem cells in the animals transplanted with syngeneic or xenogeneic cells, respectively.Conclusions - The persistence of significant iron-dependent MRI signal derived from ferumoxide-containing macrophages despite few or no viable stem cells 3 weeks after transplantation indicates that MRI of ferumoxide-labeled cells does not reliably report long-term stem cell engraftment in the heart.