Abstract
BackgroundAs 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.MethodsWe 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.ResultsThe 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.ConclusionsCM 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.
Highlights
As a large capillary network, the human placenta plays an important role throughout pregnancy
We found that primary placental cells in early pregnancy, whether CTBs or human placenta-derived mesenchymal stem cells (hPDMSCs), played more significant roles than those in full-term pregnancy
Placental cell-derived conditioned medium (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
Summary
As a large capillary network, the human placenta plays an important role throughout pregnancy. It is well known that placental villi consist of different cell types: (1) trophoblasts (syncytiotrophoblasts and cytotrophoblasts), (2) mesenchymal cells (mesenchymal stem cells, fibroblasts, mesenchymal-derived macrophages—Hoffbauer cells), and (3) fetal vascular cells (vascular smooth muscle cells, vascular pericytes, and endothelial cells) [4]. These cells are so close together that they even share a basement membrane in thirdtrimester pregnancy [8]. Proper development of the placental vasculature depends on the autocrine and paracrine signals of vascular cells and other types of placental cells [9]
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