Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (31): 4970-7975.doi: 10.12307/2021.138

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Human placenta-derived mesenchymal stem cell conditioned medium can upregulate BeWo cell viability and zonula occludens expression under hypoxia

Lin Qingfan1, Xie Yixin2, Chen Wanqing1, Ye Zhenzhong3, Chen Youfang1   

  1. 1Quanzhou Medical College, Quanzhou 362011, Fujian Province, China; 2Shishi General Hospital, Shishi 362700, Fujian Province, China; 3Fujian Genesis Stem Cell Co., Ltd., Quanzhou 362011, Fujian Province, China
  • Received:2020-06-23 Revised:2020-07-01 Accepted:2020-08-25 Online:2021-11-08 Published:2021-04-25
  • Contact: Chen Youfang, MD, Professor, Quanzhou Medical College, Quanzhou 362011, Fujian Province, China
  • About author:Lin Qingfan, Master, Quanzhou Medical College, Quanzhou 362011, Fujian Province, China
  • Supported by:
    the Maternal and Child Health Service Application Technology Collaborative Innovation Center Fund of Fujian Province, No. XJM1804 (to LQF); the Natural Science Foundation of Fujian Province, No. 2016J01422 (to CYF); the Science and Technology Project of Quanzhou, No. 2016Z005 (to LQF) 

Abstract: BACKGROUND: In recent years, mesenchymal stem cells have become a research hotspot in the field of new drug development, and their paracrine effect has also been applied in the repair evaluation experiments of a variety of tissue injured cell models, but there is no research to explore whether their conditioned medium can repair the tight junction function of human placental trophoblast cells under hypoxia.
OBJECTIVE: To demonstrate the effect of mesenchymal stem cell conditioned medium on cell viability and expression of tight junction factors in human placental choriocarcinoma trophoblast cell line BeWo under hypoxia. 
METHODS: BeWo cells were exposed to hypoxia induced by 1 000 μmol/L CoCl2 for 12 hours to construct the hypoxia model of placental barrier. For model evaluation, five indexes were measured, including cell viability and expression of hypoxia induced factors-1α, as well as three tight junction factors: zonula occludens 1, claudins 4 and claudins 8. Mesenchymal stem cell conditioned medium was added into hypoxia model to construct hypoxia intervention and reoxygenation groups. To investigate the potential mechanism of zonula occludens 1 expression recovery induced by mesenchymal stem cell conditioned medium, insulin-like growth factor 1 hypoxia intervention and treatment groups were established, and the BeWo cell viability and zonula occludens 1 expression were detected.   
RESULTS AND CONCLUSION: (1) BeWo cells viability, zonula occludens 1 and claudins 4 expression were reduced by CoCl2-mimic hypoxia, with hypoxia induced factors-1α mRNA and protein upregulation. However, the expression of claudins 8 mRNA was upregulated, and its protein was downregulated. (2) Human placenta-derived mesenchymal stem cell conditioned medium improved BeWo cells viability and recovered expression level of hypoxia induced factors-1α and zonula occludens 1 under hypoxia induced by CoCl2, but it has no effect on claudins 4. (3) Insulin like growth factor-1 intervention alleviated the inhibition of hypoxia on the viability of BeWo cells, and upregulated the expression of zonula occludens 1.

Key words: stem cells, human placenta-derived mesenchymal stem cells, conditioned medium, CoCl2, hypoxia, BeWo cells, zonula occludens 1

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