Jun Wei1, Yanqiu Yu2,3, Haiying Ma4, Shenglu Jiang5, Lili Du4, Jinfang Liu6, Xiaoyan Xu4, Xiaomei Lu4, Ling Ma4, Hua Zhu4. 1. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning Province, China. weij@sj-hospital.org. 2. Department of Pathophysiology, College of Basic Medical Science, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, China. yqyu@cmu.edu.cn. 3. Shenyang Engineering Technology R&D Center of Cell Therapy CO.LTD, No. 400-8, Zhihui 2nd Street, Hunnan District, Shenyang, 110169, Liaoning Province, China. yqyu@cmu.edu.cn. 4. Department of Pathophysiology, College of Basic Medical Science, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, China. 5. Department of Pathophysiology, Zhangjiakou University, No.P19, Pingmen Street, Qiaoxi District, Zhangjiakou, 075000, Hebei Province, China. 6. Department of Basic Medical Sciences, Basic Medical College, Shan Xi University of Traditional Chinese Medicine, No. 89, Section 1, Jinci Road, Taiyuan, 030024, Shanxi Province, China.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Authors: Jelena Krstic; Alexander Deutsch; Julia Fuchs; Martin Gauster; Tina Gorsek Sparovec; Ursula Hiden; Julian Christopher Krappinger; Gerit Moser; Katrin Pansy; Marta Szmyra; Daniela Gold; Julia Feichtinger; Berthold Huppertz Journal: Biomedicines Date: 2022-05-04