Gittenberger-de Groot A C, Vrancken Peeters M P, Mentink M M, Gourdie R G, Poelmann R E
Department of Anatomy and Embryology, Leiden University Medical Center, Netherlands.
Circ Res. 1998 Jun 1;82(10):1043-52. doi: 10.1161/01.res.82.10.1043.
The epicardium and dorsal mesocardium are known to be the source of structures that form the wall of the coronary vessels. Because mouse knockout studies have shown that proper epicardial formation is also essential for myocardial development, we have studied in detail the migration and differentiation of epicardium-derived cells (EPDCs) within the developing heart. We constructed chicken-quail chimeras by grafting the quail epicardial organ, including a piece of primordial liver, at essentially stages 16 and 17. The embryos were studied at stages 25 to 43. To detect quail-derived EPDCs, an anti-quail nucleus antibody was used in combination with several differentiation markers, eg, for muscle actin, for vascular smooth muscle cells, for procollagen-I, for quail endothelium, and for Purkinje fibers. At stages 25 to 31, EPDCs are encountered in the myocardial wall and the subendocardial region. The latter deposition is spatially facilitated as the endocardium protrudes through transient discontinuities in the myocardium to contact the subepicardial layer. Later on, at stages 32 to 43, EPDCs invaded, by way of the atrioventricular sulcus, the atrioventricular cushion tissue. The localization is apparent at the interface with the myocardium, as well as subendocardially, but never within the endocardial lining. The origin of endothelium, smooth muscle cells, and fibroblasts of the coronary vessel wall from the epicardial graft were confirmed in accordance with already published data. The functional role of the novel EPDCs in the subendocardium, myocardium, and atrioventricular cushions remains to be investigated. A close positional relationship is found with the differentiating Purkinje fibers. Furthermore, a regulatory role is postulated in the process of endocardial-mesenchymal transformation. The ultimate fate of EPDCs seems to be a cardiac fibroblast cell line involved in the formation of the fibrous heart skeleton.
已知心外膜和背侧心内膜是形成冠状血管壁结构的来源。由于小鼠基因敲除研究表明，正常的心外膜形成对心肌发育也至关重要，因此我们详细研究了发育中心脏内心外膜衍生细胞（EPDCs）的迁移和分化。我们通过在第16和17阶段移植包括一块原始肝脏的鹌鹑心外膜器官构建了鸡-鹌鹑嵌合体。在第25至43阶段对胚胎进行研究。为了检测鹌鹑来源的EPDCs，使用抗鹌鹑核抗体并结合几种分化标志物，例如用于肌肉肌动蛋白、血管平滑肌细胞、原胶原-I、鹌鹑内皮细胞和浦肯野纤维的标志物。在第25至31阶段，在心肌壁和心内膜下区域可发现EPDCs。随着心内膜通过心肌中的短暂间断突出以接触心外膜下层，后者的沉积在空间上得到促进。后来，在第32至43阶段，EPDCs通过房室沟侵入房室垫组织。其定位在与心肌的界面以及心内膜下明显可见，但从未在内皮衬里内。根据已发表的数据证实了冠状血管壁的内皮细胞、平滑肌细胞和成纤维细胞来自心外膜移植。新型EPDCs在心内膜下、心肌和房室垫中的功能作用仍有待研究。发现与分化中的浦肯野纤维存在密切的位置关系。此外，推测其在心脏内膜-间充质转化过程中具有调节作用。EPDCs的最终命运似乎是参与纤维性心脏骨架形成的心脏成纤维细胞系。
