As a large capillary network, the human placenta plays an important role throughout pregnancy. Placental vascular development is complex and delicate and involves many types of placental cells, such as trophoblasts, and mesenchymal stem cells. There has been no systematic, comparative study on the roles of these two groups of placental cells and the whole placental tissue in the placental angiogenesis. In this study, primary cytotrophoblasts (CTBs) from early pregnancy and primary human placenta-derived mesenchymal stem cells (hPDMSCs) from different stages of pregnancy were selected as the cell research objects, and full-term placental tissue was selected as the tissue research object to detect the effects of their conditioned medium (CM) on human umbilical vein endothelial cell (HUVEC) angiogenesis. We successfully isolated primary hPDMSCs and CTBs, collected CM from these placental cells and sub-cultured placental tissue, and then evaluated the effects of the CM on a series of angiogenic processes in HUVECs in vitro. Furthermore, we measured the levels of angiogenic factors in the CM of placental cells or tissue by an angiogenesis antibody array. The results showed that not only placental cells but also sub-cultured placental tissue, to some extent, promoted HUVEC angiogenesis in vitro by promoting proliferation, adhesion, migration, invasion, and tube formation. We also found that primary placental cells in early pregnancy, whether CTBs or hPDMSCs, played more significant roles than those in full-term pregnancy. Placental cell-derived CM collected at 24 h or 48 h had the best effect, and sub-cultured placental tissue-derived CM collected at 7 days had the best effect among all the different time points. The semiquantitative angiogenesis antibody array showed that 18 of the 43 angiogenic factors had obvious spots in placental cell-derived CM or sub-cultured placental tissue-derived CM, and the levels of 5 factors (including CXCL-5, GRO, IL-6, IL-8, and MCP-1) were the highest in sub-cultured placental tissue-derived CM. CM obtained from placental cells (primary CTBs or hPDMSCs) or sub-cultured placental tissue contained proangiogenic factors and promoted HUVEC angiogenesis in vitro. Therefore, our research is helpful to better understand placental angiogenesis regulation and provides theoretical support for the clinical application of placental components, especially sub-cultured placental tissue-derived CM, in vascular tissue engineering and clinical treatments.

中文翻译：

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来自原代细胞滋养细胞，原代胎盘的间充质干细胞或传代培养的胎盘组织的条件培养基在体外促进了HUVEC血管生成

作为大型毛细血管网，人胎盘在整个怀孕过程中起着重要作用。胎盘血管发育复杂而脆弱，涉及许多类型的胎盘细胞，例如滋养细胞和间充质干细胞。尚未对这两组胎盘细胞和整个胎盘组织在胎盘血管生成中的作用进行系统的比较研究。在这项研究中，来自妊娠早期的原代细胞滋养细胞（CTB）和来自妊娠不同阶段的原代人胎盘来源的间充质干细胞（hPDMSC）被选为细胞研究对象，并选择足月胎盘组织作为组织研究对象。检测其条件培养基（CM）对人脐静脉内皮细胞（HUVEC）血管生成的影响。我们成功分离了原代hPDMSC和CTB，从这些胎盘细胞和传代培养的胎盘组织中收集了CM，然后评估了CM对HUVEC体外一系列血管生成过程的影响。此外，我们通过血管生成抗体阵列测量了胎盘细胞或组织中CM的血管生成因子水平。结果表明，不仅胎盘细胞，而且胎盘继代培养组织在一定程度上还通过促进增殖，粘附，迁移，侵袭和管形成而促进了HUVEC血管生成。我们还发现，无论是CTB还是hPDMSC，怀孕初期的胎盘细胞都比足月怀孕的胎盘细胞起着更重要的作用。在24小时或48小时收集的胎盘细胞衍生CM效果最好，在所有不同时间点收集的7天传代培养的胎盘组织来源的CM效果最佳。半定量血管生成抗体阵列显示，在43种血管生成因子中，有18种在胎盘细胞衍生的CM或继代培养的胎盘组织衍生的CM中有明显斑点，并且5种因子的水平（包括CXCL-5，GRO，IL-6， IL-8和MCP-1）在胎盘组织衍生的CM中最高。从胎盘细胞（原代CTB或hPDMSC）或传代培养的胎盘组织获得的CM含有促血管生成因子，并在体外促进HUVEC血管生成。因此，我们的研究有助于更好地了解胎盘血管生成的调控，并为胎盘成分的临床应用提供理论支持，尤其是继代培养的胎盘组织来源的CM，