Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, United States of America.
PLoS One. 2013 Jul 9;8(7):e68528. doi: 10.1371/journal.pone.0068528. Print 2013.
Stage specific embryonic antigen 1+ (SSEA1+) cells have been described as the most primitive mesenchymal progenitor cell in the bone marrow. Cardiac injury mobilizes SSEA1+ cells into the peripheral blood but their in vivo function has not been characterized.
We generated animals with chimeric bone marrow to determine the fate and function of bone marrow SSEA1+ cells in response to acute cardiac pressure overload.
Lethally irradiated mice were transplanted with normal bone marrow where the wild-type SSEA1+ cells were replaced with green fluorescent protein (GFP) SSEA1+ cells. Cardiac injury was induced by trans-aortic constriction (TAC). We identified significant GFP+ cell engraftment into the myocardium after TAC. Bone marrow GFP+ SSEA1 derived cells acquired markers of endothelial lineage, but did not express markers of c-kit+ cardiac progenitor cells. The function of bone marrow SSEA1+ cells after TAC was determined by transplanting lethally irradiated mice with bone marrow depleted of SSEA1+ cells (SSEA1-BM). The cardiac function of SSEA1-BM mice declined at a greater rate after TAC compared to their complete bone marrow transplant counterparts and was associated with decreased bone marrow cell engraftment and greater vessel rarefication in the myocardium.
These results provide evidence for the recruitment of endogenous bone marrow SSEA1+ cells to the myocardium after TAC. We demonstrate that, in vivo, bone marrow SSEA1+ cells have the differentiation potential to acquire endothelial lineage markers. We also show that bone marrow SSEA1+ deficiency is associated with a reduced compensatory capacity to cardiac pressure overload, suggesting their importance in cardiac homeostasis. These data demonstrate that bone marrow SSEA1+ cells are critical for sustaining vascular density and cardiac repair to pressure overload.
阶段特异性胚胎抗原 1+（SSEA1+）细胞已被描述为骨髓中最原始的间充质祖细胞。心脏损伤会将 SSEA1+细胞动员到外周血中，但它们的体内功能尚未得到表征。
我们生成嵌合骨髓动物，以确定骨髓 SSEA1+细胞在急性心脏压力超负荷下的命运和功能。
致死性辐照的小鼠接受正常骨髓移植，其中野生型 SSEA1+细胞被绿色荧光蛋白（GFP）SSEA1+细胞取代。通过主动脉缩窄（TAC）诱导心脏损伤。我们发现 TAC 后 GFP+细胞明显植入心肌。骨髓 GFP+SSEA1 衍生细胞获得内皮谱系标志物，但不表达 c-kit+心脏祖细胞标志物。通过移植 SSEA1+细胞耗尽的骨髓（SSEA1-BM）来确定 TAC 后骨髓 SSEA1+细胞的功能。与完全骨髓移植对照相比，SSEA1-BM 小鼠在 TAC 后心脏功能下降速度更快，与骨髓细胞植入减少和心肌中血管稀疏增加有关。
这些结果为 TAC 后内源性骨髓 SSEA1+细胞募集到心肌提供了证据。我们证明，在体内，骨髓 SSEA1+细胞具有获得内皮谱系标志物的分化潜力。我们还表明，骨髓 SSEA1+缺乏与心脏压力超负荷的代偿能力降低有关，这表明它们在心脏稳态中的重要性。这些数据表明，骨髓 SSEA1+细胞对于维持血管密度和心脏修复对压力超负荷至关重要。
