Effect of Human Bone Marrow Mesenchymal Stem Cells with Ectopic High OCT4 Expression on T Lymphocyte Function.
10.19746/j.cnki.issn.1009-2137.2023.05.043
- Author:
Xiao-Ping GUO
1
;
Yan-Fei CHEN
1
;
Ping CHEN
1
;
Jin PAN
1
;
Pei-Ting YING
1
;
Ning ZHAO
1
;
Yong-Min TANG
2
Author Information
1. Division/Center of Pediatric Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, The Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou 310003, Zhejiang Province, China.
2. Division/Center of Pediatric Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, The Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou 310003, Zhejiang Province, China. E-mail: y_m_tang@zju.edu.cn.
- Publication Type:Journal Article
- Keywords:
OCT4;
cytokine;
human bone marrow mesenchymal stem cells;
immuno-regulation;
transcription factor
- MeSH:
Child;
Humans;
Bone Marrow Cells;
CD8-Positive T-Lymphocytes/metabolism*;
Cell Proliferation;
Cells, Cultured;
Interleukin-2;
Interleukin-6/metabolism*;
Leukocytes, Mononuclear/metabolism*;
Lymphocyte Activation;
Mesenchymal Stem Cells;
Tumor Necrosis Factor-alpha/metabolism*
- From:
Journal of Experimental Hematology
2023;31(5):1523-1530
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the effect of human bone marrow mesenchymal stem cells (MSCs) with ectopic high OCT4 expression on T-cell proliferation, activation and secretion in vitro.
METHODS:Peripheral blood mononuclear cells were isolated from healthy children. Anti-CD3 and anti-CD28 monoclonal antibodies were used to activate T lymphocytes, which were stimulated by interleukin (IL)-2 for one week in vitro. Then MSCs with ectopic high OCT4 expression (MSC-OCT4) were co-cultured with activated T lymphocytes. After one week of co-culture, the supernatant was collected and the levels of Th1/Th2 cytokines [IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ] were determined by flow cytometry. The lymphocytes after one week of co-culture were collected and counted by Countstar software. After the proportions of activated/inactivated T cell subsets were determined by flow cytometry, the absolute lymphocyte counts were calculated and expressed as mean ± standard deviation.
RESULTS:Compared with control T cell alone culture group, the proliferation of CD3+ T cells, CD3+CD4+ T cells, and CD3+CD8+ T cells were significantly inhibited in MSC group and MSC-OCT4 group. Compared with MSC, MSC-OCT4 could inhibit CD3+CD8+ T cell proliferation better (P =0.049), and mainly inhibited early T cell activation. Compared with control T cell alone culture group, the levels of IL-2 and INF-γ were significantly down-regulated both in MSC group and MSC-OCT4 group.After co-culture with T cells for one week, the level of IL-6 significantly increased in MSC group and MSC-OCT4 group compared with that before co-culture. Compared with control MSC group, MSC-OCT4 group had higher viable cell numbers after 1 week of co-culture (P =0.019), and could resist the inhibition of proliferation by higher concentration of mitomycin C.
CONCLUSION:Both MSC and MSC-OCT4 can inhibit the proliferation and activation of IL-2-stimulated T cells in vitro. After overexpression of OCT4, MSC has better proliferation ability in vitro and can inhibit the proliferation of CD3+CD8+ T cells more effectively, which may have a better and more lasting immunosuppressive ability to regulate the balance of Th1/Th2.
