Interleukin-10 from transplanted bone marrow mononuclear cells contributes to cardiac protection after myocardial infarction
Interleukin-10 from transplanted bone marrow mononuclear cells contributes to cardiac protection after myocardial infarction
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DOI：
10.1161/circresaha.108.178475
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发表时间：
2008-07-18
影响因子：
20.1
通讯作者：
Dimmeler, Stefanie
中科院分区：
文献类型：
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作者：
Burchfield, Jana S.;Iwasaki, Masayoshi;Dimmeler, Stefanie
骨髓单核细胞（BM-MNCs）已被成功地用于改善心肌梗死（MI）后左心室（LV）功能的治疗。有研究表明，来自BM-MNCs的旁分泌因子可能是介导心脏保护的关键机制。我们之前进行了微阵列分析，发现与成人内皮细胞和CD14（+）细胞相比，人类祖细胞中的多益细胞因子白细胞介素(IL)-10高度上调。此外，BM-MNCs分泌大量的IL-10， IL-10可以从移植到梗死小鼠心脏的祖细胞中检测到。具体而言，与注射稀释剂或IL-10敲除了的BM-MNCs相比，心肌内注射野生型BM-MNCs导致左室舒张末期压（LVEDP）和左室收缩末期体积（LVESV）显著降低。此外，与注射稀释剂或IL-10敲除的BM-MNCs相比，心肌内注射野生型BM-MNCs导致脑卒中容量（SV）和压力随时间发展的速率（+dP/dt）显著增加。移植细胞提供的il -10依赖性改善不是由梗死面积减少、中性粒细胞浸润或毛细血管密度减少引起的，而是与T淋巴细胞积聚减少、反应性肥大和心肌胶原沉积有关。这些结果表明，BM-MNCs介导心肌梗死后的心脏保护，这至少部分依赖于IL-10。
Bone marrow mononuclear cells (BM-MNCs) have successfully been used as a therapy for the improvement of left ventricular (LV) function after myocardial infarction (MI). It has been suggested that paracrine factors from BM-MNCs may be a key mechanism mediating cardiac protection. We previously performed microarray analysis and found that the pleiotropic cytokine interleukin (IL)-10 was highly upregulated in human progenitor cells in comparison with adult endothelial cells and CD14(+) cells. Moreover, BM-MNCs secrete significant amounts of IL-10, and IL-10 could be detected from progenitor cells transplanted in infarcted mouse hearts. Specifically, intramyocardial injection of wild-type BM-MNCs led to a significant decrease in LV end-diastolic pressure (LVEDP) and LV end-systolic volume (LVESV) compared to hearts injected with either diluent or IL-10 knock-out BM-MNCs. Furthermore, intramyocardial injection of wild-type BM-MNCs led to a significant increase in stroke volume (SV) and rate of the development of pressure over time (+dP/dt) compared to hearts injected with either diluent or IL-10 knock-out BM-MNCs. The IL-10-dependent improvement provided by transplanted cells was not caused by reduced infarct size, neutrophil infiltration, or capillary density, but rather was associated with decreased T lymphocyte accumulation, reactive hypertrophy, and myocardial collagen deposition. These results suggest that BM-MNCs mediate cardiac protection after myocardial infarction and this is, at least in part, dependent on IL-10.