Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction
Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction
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DOI：
10.1161/01.res.0000150856.47324.5b
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发表时间：
2004-12-10
影响因子：
20.1
通讯作者：
Ratajczak, MZ
中科院分区：
文献类型：
--
作者：
Kucia, M;Dawn, B;Ratajczak, MZ
骨髓（BM）来源的细胞参与心脏再生的概念仍然存在很大争议，并且所涉及的特定细胞类型的身份仍然未知。在这项研究中，我们报告出生后 BM 包含表达早期心脏谱系标记物（Nkx2.5/Csx、GATA-4 和 MEF2C）的移动细胞库。这些细胞在从年轻小鼠身上采集的骨髓中大量存在，但它们的丰度随着年龄的增长而减少；此外，这些细胞对运动形态发生素 SDF-1、HGF 和 LIF 梯度的响应随着年龄的增长而变化。 FACS分析结合mRNA和蛋白质水平上的早期心脏标志物分析，揭示表达这些标志物的细胞存在于小鼠的非贴壁、非造血CXCR4(+)/Sca-1(+)/lin(-)/CD45(-)单核细胞(MNC)部分和人类的CXCR4(+)/CD34(+)/AC133(+)/CD45(-) BMMNC部分中。这些细胞在心肌梗塞后动员到外周血中，并以 SDF-1-CXCR4、HGF-c-Met 和 LIF-LIF-R 依赖性方式趋化至梗塞心肌。据我们所知，这是首次证明出生后骨髓中含有表达心脏分化标记物的非造血细胞群。我们认为这些潜在的心脏祖细胞可能解释了 BM 的心肌再生作用。目前的研究结果提供了一种新的范式，可以调和当前的争议，并为研究使用骨髓来源的心脏祖细胞进行心肌再生提供依据。
The concept that bone marrow ( BM)-derived cells participate in cardiac regeneration remains highly controversial and the identity of the specific cell type(s) involved remains unknown. In this study, we report that the postnatal BM contains a mobile pool of cells that express early cardiac lineage markers (Nkx2.5/Csx, GATA-4, and MEF2C). These cells are present in significant amounts in BM harvested from young mice but their abundance decreases with age; in addition, the responsiveness of these cells to gradients of motomorphogens SDF-1, HGF, and LIF changes with age. FACS analysis, combined with analysis of early cardiac markers at the mRNA and protein levels, revealed that cells expressing these markers reside in the nonadherent, nonhematopoietic CXCR4(+)/Sca-1(+)/lin(-)/CD45(-) mononuclear cell (MNC) fraction in mice and in the CXCR4(+)/CD34(+)/AC133(+)/CD45(-) BMMNC fraction in humans. These cells are mobilized into the peripheral blood after myocardial infarction and chemoattracted to the infarcted myocardium in an SDF-1-CXCR4-, HGF-c-Met-, and LIF-LIF-R-dependent manner. To our knowledge, this is the first demonstration that the postnatal BM harbors a nonhematopoietic population of cells that express markers for cardiac differentiation. We propose that these potential cardiac progenitors may account for the myocardial regenerative effects of BM. The present findings provide a novel paradigm that could reconcile current controversies and a rationale for investigating the use of BM-derived cardiac progenitors for myocardial regeneration.