Effect of Chemotherapeutic Drug-Induced Damage of Bone Marrow Stroma Cells on Normal Hematopoietic Cells.
10.7534/j.issn.1009-2137.2019.01.038
- Author:
Yi-Hui LI
1
;
Zhe LIU
1
;
Huan LI
1
;
Ying-Xi XU
1
;
Hai-Yan XING
1
;
Ke-Jing TANG
1
;
Zheng TIAN
1
;
Min WANG
1
;
Qing RAO
2
Author Information
1. State Key Laboratory of Experimental Hematology, Institute of Hematology &Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
2. State Key Laboratory of Experimental Hematology, Institute of Hematology &Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.E-mail: raoqing@ihcams.ac.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Bone Marrow;
Bone Marrow Cells;
Cells, Cultured;
Hematopoietic Stem Cell Transplantation;
Hematopoietic Stem Cells;
Mesenchymal Stem Cells;
Mice;
Stromal Cells
- From:
Journal of Experimental Hematology
2019;27(1):233-238
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the effect of damage of bone marrow stroma cells induced by chemotherapeutic drug on the function of normal hematopoitic cells.
METHODS:Senescence cells were detected by flow cytometry after SA-β-gal staining; real-time PCR was used to detect the expression of a serial molecules in bone marrow stromal cell line OP9 cells; the expression of γ-H2AX was determined by flow cytometry after histone γ-H2AX staining; the colony forming ability of hematopoietic cells was tested by colony formation assay.
RESULTS:The percentage of senescence cells in OP9 cells after DNR treatment was 2.24 times as much as that in untreated OP9 cells (P<0.05). Compared with normal OP9 cells, the expression levels of IL-6 and TNF-alpha in DNR-treated OP9 cells increased by 2.73 times (P<0.01) and 0.56 times (P<0.01), and the expression levels of N-cadherin, alpha smooth muscle actin (alpha-SMA), angiopoietin1 (Angpt1) and osteopontin (OPN) decreased by 69.54%(P<0.01),63.90%(P<0.01),87.41%(P<0.01)and 42.78%(P<0.01)respectively. After the co-culture with DNR-treated OP9 cells, the colony formation of normal hematopoietic cells decreased by 47.10% than that co-cultured with untreated OP9 cells (P< 0.05), meanwhile, the percentage of γ-H2AX+ cells in normal hematopoietic cells increased by 2.19 times (P<0.05).
CONCLUSION:After treatment with DNR, the senescence cell number of OP9 cells sgnificantly increases; the expression of TNF-α and IL-6 is up-regulated, while the expression of α-SMA, Angpt-1 and OPN is down-regulated as compared with normal OP9 cells. In addition, after co-culture of DNR-treated OP9 cells with normal hematopoietic cells, the colony formation ability of hematopoietic cells decreases and the genome instability of hematopoietic cells increases as compared with normal hematopoietic cells.