Kucia Magda, Dawn Buddhadeb, Hunt Greg, Guo Yiru, Wysoczynski Marcin, Majka Marcin, Ratajczak Janina, Rezzoug Francine, Ildstad Suzanne T, Bolli Roberto, Ratajczak Mariusz Z
Stem Cell Biology Program, University of Louisville, Louisville, Ken 40202, USA.
Circ Res. 2004 Dec 10;95(12):1191-9. doi: 10.1161/01.RES.0000150856.47324.5b. Epub 2004 Nov 18.
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.
骨髓（BM）来源的细胞参与心脏再生这一概念仍极具争议，且所涉及的特定细胞类型的身份尚不清楚。在本研究中，我们报告出生后的骨髓中含有一群可移动的细胞，这些细胞表达早期心脏谱系标志物（Nkx2.5/Csx、GATA - 4和MEF2C）。这些细胞在从小鼠采集的骨髓中大量存在，但它们的丰度会随着年龄增长而降低；此外，这些细胞对趋化因子SDF - 1、HGF和LIF梯度的反应性也会随年龄变化。流式细胞术分析结合mRNA和蛋白质水平的早期心脏标志物分析表明，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）组分中，以及人类的CXCR4 + /CD34 + /AC133 + /CD45 - 骨髓单个核细胞（BMMNC）组分中。这些细胞在心肌梗死后被动员到外周血中，并以SDF - 1 - CXCR4 - 、HGF - c - Met - 和LIF - LIF - R依赖的方式被吸引到梗死心肌。据我们所知，这是首次证明出生后的骨髓中存在一群非造血细胞，它们表达心脏分化标志物。我们认为这些潜在的心脏祖细胞可能解释了骨髓的心肌再生作用。目前的研究结果提供了一个新的范例，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理论依据。
