Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (24): 3780-3787.doi: 10.12307/2023.673

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Biological characteristics of tumor necrosis factor-alpha-primed human umbilical cord mesenchymal stem cells

Chen Zili1, Cao Ning2, Xu Meng2, Jiang Yan2, Ji Meichao2, Zheng Yangyang2, Yang Lili1   

  1. 1Department of Obstetrics and Gynecology, Tianjin Fifth Central Hospital (Peking University Binhai Hospital), Tianjin 300450, China; 2Tingo Regenerative Medicine (Tianjin) Technology Co., Ltd., Tianjin 300450, China 
  • Received:2022-08-02 Accepted:2022-10-12 Online:2023-08-28 Published:2023-01-18
  • Contact: Yang Lili, Attending physician, Department of Obstetrics and Gynecology, Tianjin Fifth Central Hospital (Peking University Binhai Hospital), Tianjin 300450, China
  • About author:Chen Zili, Chief physician, Department of Obstetrics and Gynecology, Tianjin Fifth Central Hospital (Peking University Binhai Hospital), Tianjin 300450, China Cao Ning, Master, Senior engineer, Tingo Regenerative Medicine (Tianjin) Technology Co., Ltd., Tianjin 300450, China
  • Supported by:
    the Science and Technology Project of Tianjin Binhai New Area Health and Family Planning Commission, No. 2015BWKZ003 (to CZL)

Abstract: BACKGROUND: In some preclinical and clinical studies, human umbilical cord mesenchymal stem cells have shown promising therapeutic results but limited efficacy. Therefore, enhancing the function of human umbilical cord mesenchymal stem cells by priming provides a new idea for the development of stem cell culture technology.  
OBJECTIVE: To explore the changes of biological properties and mechanism of human umbilical cord mesenchymal stem cells primed with inflammatory factor tumor necrosis factor-α.
METHODS: The human umbilical cord mesenchymal stem cells were cultured to the sixth generation and primed with inflammatory factor tumor necrosis factor-α. The changes of immunomodulatory ability, anti-inflammatory function, surface markers, doubling time, and adipogenesis and osteogenesis ability were evaluated in control group and tumor necrosis factor-α-primed group of human umbilical cord mesenchymal stem cells. In addition, the transcriptome analysis of the two groups was compared to illustrate the precise mechanism.  
RESULTS AND CONCLUSION: (1) Compared with the control group, different mass concentrations of tumor necrosis factor-α-primed human umbilical cord mesenchymal stem cells inhibited T cell proliferation and promoted Treg cell proliferation significantly. The effect of 1 ng/mL tumor necrosis factor-α was the most significant. (2) Compared with the control group, different mass concentrations of tumor necrosis factor-α-primed human umbilical cord mesenchymal stem cells released lower levels of tumor necrosis factor-α and higher levels of interleukin-10 in inflammatory model in vitro, and their anti-inflammatory ability was significantly enhanced. (3) There was no significant difference in cell multiplication time and surface marker expression between the control group and tumor necrosis factor-α-primed group, and both groups had strong osteogenic and lipogenic differentiation abilities. (4) Transcriptome changes between control group and tumor necrosis factor-α-primed group were mainly reflected in the activation of nuclear factor-κB signaling pathway and tumor necrosis factor-α signaling pathway. (5) These results indicated that tumor necrosis factor-α-primed human umbilical cord mesenchymal stem cells significantly enhanced their immunomodulatory and anti-inflammatory functions.

Key words: umbilical cord mesenchymal stem cell, inflammatory factor, prime, immune regulation, anti-inflammatory function, quality attribute, transcriptome expression profile, differentially expressed gene

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