Department of Cell Biology, Institute of Basic Medical Sciences, Beijing, China.
Dev Dyn. 2011 Jan;240(1):65-74. doi: 10.1002/dvdy.22490.
Mesenchymal stem cells (MSCs) represent powerful tools for regenerative medicine for their differentiation and migration capacity. However, ontogeny and migration of MSCs in mammalian mid-gestation conceptus is poorly understood. We identified canonical MSCs in the mouse embryonic day (E) 11.5 dorsal aorta (DA). They possessed homogenous immunophenotype (CD45(-)CD31(-)Flk-1(-)CD44(+)CD29(+)), expressed perivascular markers (α-SMA(+)NG2(+)PDGFRβ(+)PDGFRα(+)), and had tri-lineage differentiation potential (osteoblasts, adipocytes, and chondrocytes). Of interest, MSCs were also detected in E12.5-E13.5 embryonic circulation, 24 hr later than in DA, suggesting migration like hematopoietic stem cells. Functionally, E12.5 embryonic blood could trigger efficient migration of DA-MSCs through platelet-derived growth factor (PDGF) receptor-, transforming growth factor-beta receptor-, but not basic fibroblast growth factor receptor-mediated signaling. Moreover, downstream JNK and AKT signaling pathway played important roles in embryonic blood- or PDGF-mediated migration of DA-derived MSCs. Taken together, these results revealed that clonal MSCs developed in the mouse DA. More importantly, the embryonic circulation, in addition to its conventional transporting roles, could modulate migration of MSC during early embryogenesis.
间充质干细胞 (MSCs) 因其分化和迁移能力而成为再生医学的有力工具。然而，哺乳动物中期胚胎中 MSCs 的发生和迁移仍知之甚少。我们在小鼠胚胎第 11.5 天 (E) 的背主动脉 (DA) 中鉴定出了典型的 MSCs。它们具有同质的免疫表型 (CD45(-)CD31(-)Flk-1(-)CD44(+)CD29(+))，表达血管周细胞标志物 (α-SMA(+)NG2(+)PDGFRβ(+)PDGFRα(+))，并具有三系分化潜能 (成骨细胞、脂肪细胞和成软骨细胞)。有趣的是，MSCs 也在 E12.5-E13.5 胚胎循环中被检测到，比在 DA 中晚 24 小时，这表明它们像造血干细胞一样迁移。功能上，E12.5 胚胎血液可以通过血小板衍生生长因子 (PDGF) 受体、转化生长因子-β受体，但不是碱性成纤维细胞生长因子受体介导的信号通路触发 DA-MSCs 的有效迁移。此外，下游 JNK 和 AKT 信号通路在胚胎血液或 PDGF 介导的 DA 来源 MSCs 迁移中发挥重要作用。综上所述，这些结果表明克隆 MSC 是在小鼠 DA 中发育而来的。更重要的是，胚胎循环除了其传统的运输作用外，还可以调节早期胚胎发生中 MSC 的迁移。
