Rationale: Myocardial infarction is a major cause of adult mortality worldwide. The origin(s) of cardiac fibroblasts that constitute the postinfarct scar remain controversial, in particular the potential contribution of bone marrow lineages to activated fibroblasts within the scar.

Objective: The aim of this study was to establish the origin(s) of infarct fibroblasts using lineage tracing and bone marrow transplants and a robust marker for cardiac fibroblasts, the Collagen1a1-green fluorescent protein reporter.

Methods and Results: Using genetic lineage tracing or bone marrow transplant, we found no evidence for collagen-producing fibroblasts derived from hematopoietic or bone marrow lineages in hearts subjected to permanent left anterior descending coronary artery ligation. In fact, fibroblasts within the infarcted area were largely of epicardial origin. Intriguingly, collagen-producing fibrocytes from hematopoietic lineages were observed attached to the epicardial surface of infarcted and sham-operated hearts in which a suture was placed around the left anterior descending coronary artery.

Conclusions: In this controversial field, our study demonstrated that the vast majority of infarct fibroblasts were of epicardial origin and not derived from bone marrow lineages, endothelial-to-mesenchymal transition, or blood. We also noted the presence of collagen-producing fibrocytes on the epicardial surface that resulted at least in part from the surgical procedure.

中文翻译：

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梗死成纤维细胞并非源自骨髓谱系的新颖性和意义

理由：心肌梗塞是全球成人死亡的主要原因。构成梗塞后瘢痕的心脏成纤维细胞的起源仍存在争议，尤其是骨髓谱系对瘢痕内活化的成纤维细胞的潜在贡献。

目的：本研究的目的是利用谱系示踪和骨髓移植以及心肌成纤维细胞的可靠标记物Collagen1a1绿色荧光蛋白报道基因，确定梗死性成纤维细胞的起源。

方法和结果：使用遗传谱系示踪或骨髓移植，我们没有发现永久性左冠状动脉前降支结扎心脏中造血或骨髓谱系产生胶原的成纤维细胞的证据。实际上，梗塞区域内的成纤维细胞主要是心外膜起源的。有趣的是，观察到来自造血谱系的产生胶原的纤维细胞附着在梗死的和假手术的心脏的心外膜表面，在心脏的左前降支周围缝合了缝线。

结论：在这个有争议的领域，我们的研究表明，绝大多数梗死性成纤维细胞是心外膜起源的，而不是源自骨髓谱系，内皮向间充质转化或血液。我们还注意到心外膜表面上存在胶原蛋白生成的纤维细胞的存在，这至少部分是由于外科手术造成的。