Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Stem Cells. 2012 Sep;30(9):1911-24. doi: 10.1002/stem.1164.
Umbilical cord blood-derived endothelial colony-forming cells (UCB-ECFC) show utility in neovascularization, but their contribution to osteogenesis has not been defined. Cocultures of UCB-ECFC with human fetal-mesenchymal stem cells (hfMSC) resulted in earlier induction of alkaline phosphatase (ALP) (Day 7 vs. 10) and increased mineralization (1.9×; p < .001) compared to hfMSC monocultures. This effect was mediated through soluble factors in ECFC-conditioned media, leading to 1.8-2.2× higher ALP levels and a 1.4-1.5× increase in calcium deposition (p < .01) in a dose-dependent manner. Transcriptomic and protein array studies demonstrated high basal levels of osteogenic (BMPs and TGF-βs) and angiogenic (VEGF and angiopoietins) regulators. Comparison of defined UCB and adult peripheral blood ECFC showed higher osteogenic and angiogenic gene expression in UCB-ECFC. Subcutaneous implantation of UCB-ECFC with hfMSC in immunodeficient mice resulted in the formation of chimeric human vessels, with a 2.2-fold increase in host neovascularization compared to hfMSC-only implants (p = .001). We conclude that this study shows that UCB-ECFC have potential in therapeutic angiogenesis and osteogenic applications in conjunction with MSC. We speculate that UCB-ECFC play an important role in skeletal and vascular development during perinatal development but less so in later life when expression of key osteogenesis and angiogenesis genes in ECFC is lower.
脐带血来源的内皮祖细胞（UCB-ECFC）在血管新生方面具有应用价值，但它们在成骨方面的作用尚未确定。将 UCB-ECFC 与人类胎儿间充质干细胞（hfMSC）共培养可使碱性磷酸酶（ALP）更早诱导（第 7 天比第 10 天），矿化程度增加（1.9 倍；p<.001）与 hfMSC 单培养相比。这种效应是通过 ECFC 条件培养基中的可溶性因子介导的，导致 ALP 水平升高 1.8-2.2 倍，钙沉积增加 1.4-1.5 倍（p<.01），呈剂量依赖性。转录组和蛋白质芯片研究表明，成骨（BMP 和 TGF-βs）和血管生成（VEGF 和血管生成素）调节剂的基础水平较高。与成人外周血 ECFC 相比，定义的 UCB 和成人外周血 ECFC 表现出更高的成骨和血管生成基因表达。将 UCB-ECFC 与 hfMSC 皮下植入免疫缺陷小鼠中，可形成嵌合人血管，与仅植入 hfMSC 的植入物相比，宿主新生血管化增加了 2.2 倍（p=0.001）。我们得出结论，本研究表明 UCB-ECFC 具有与 MSC 结合在治疗性血管生成和成骨应用中的潜力。我们推测，UCB-ECFC 在围产期发育过程中在骨骼和血管发育中起重要作用，但在生命后期作用较小，此时 ECFC 中成骨和血管生成关键基因的表达水平较低。
