Cx43修饰人脐血源基质细胞输注阻抑白血病MRD小鼠造血干细胞移植后复发

邓怡; 杨世杰; 贾延辉; 高蕾; 张诚; 刘耀; 司维柯; 张曦

doi:10.16016/j.1000-5404.201610138

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Cx43修饰人脐血源基质细胞输注阻抑白血病MRD小鼠造血干细胞移植后复发

基础医学 | 更新时间：2026-01-09

- Cx43修饰人脐血源基质细胞输注阻抑白血病MRD小鼠造血干细胞移植后复发
- Cx43 modified human umbilical cord blood-derived stromal cells prevent relapse in minimal residual disease model of mice after hematopoietic stem cells transplantation
- 第三军医大学学报 2017年39卷第9期页码：813-820
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金面上项目(81070388);国家自然科学基金面上项目(81270569);重庆市基础与前沿研究计划重点项目(CSTC2015jcyjBX0077);全军后勤科研“十二五”计划重大项目(AWS14C014)
- DOI：10.16016/j.1000-5404.201610138
  中图分类号：
- 收稿：2016-10-21，
  
  纸质出版：2017-05-15
- 稿件说明：
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邓怡, 杨世杰, 贾延辉, 等. Cx43修饰人脐血源基质细胞输注阻抑白血病MRD小鼠造血干细胞移植后复发[J]. 第三军医大学学报, 2017,39(9):813-820.

Yi Deng, Shijie Yang, Yanhui Jia, et al. Cx43 modified human umbilical cord blood-derived stromal cells prevent relapse in minimal residual disease model of mice after hematopoietic stem cells transplantation[J]. Journal of Third Military Medical University, 2017, 39(9): 813-820.
邓怡, 杨世杰, 贾延辉, 等. Cx43修饰人脐血源基质细胞输注阻抑白血病MRD小鼠造血干细胞移植后复发[J]. 第三军医大学学报, 2017,39(9):813-820. DOI： 10.16016/j.1000-5404.201610138.

Yi Deng, Shijie Yang, Yanhui Jia, et al. Cx43 modified human umbilical cord blood-derived stromal cells prevent relapse in minimal residual disease model of mice after hematopoietic stem cells transplantation[J]. Journal of Third Military Medical University, 2017, 39(9): 813-820. DOI： 10.16016/j.1000-5404.201610138.

摘要

Abstract

Objective

To investigate the effect of connexin 43 (Cx43) modified human umbilical cord blood-derived stromal cells (hUCBDSCs) on the apoptosis of mouse leukemia cell line L615s and on pathoprogression in minimal residual disease (MRD) model of mice.

Methods

Adenoviral plasmid Ad-Cx43-GFP was used to up-regulate the Cx43 expression in hUCBDSCs. The apoptotic rate of L615 cells co-cultured with Cx43-hUCBDSCs was determined by Annexin V/PI apoptosis detection kit. A mouse MRD model was generated through tail venous injection of with 1×10

GFP-L615 cells. Bone marrow (BM) and Cx43+hUCBDSCs+BM transplantation were performed in the MRD mice

and the model mice served as control. Peripheral blood cell count

BM pathological smears

histopathology and the expression of Cx43 in the BM were examined.

Results

Ad-Cx43-GFP transfection significantly increased the expression of Cx43 in the hUCBDSCs at both mRNA and protein levels. The apoptotic rate of L615 cells was significantly higher in the Cx43+hUCBDSCs co-culture model than L615 cells cultured alone [(8.93±1.24)%

(3.53±0.13)%

0.01

]

. Cx43+hUCBDSCs+BM transplantation resulted in obvious recoveries in the peripheral white blood cell count (WBC) and platelet count (PLT)

with the counts almost reaching normal values in 17 d later. Whereas

the BM transplantation group showed delayed recoveries in peripheral WBC and PLT

and the counts were still lower than those of normal group in 17 d. The count of different bone marrow cells in BM pathological smears showed that the percentage of original cells was obviously decreased in the C

x43+hUCBDSCs+BM group than the BM group [(7.67±1.25)%

(56.33±1.25)%

0.01

]

. The pathological observation showed an obviously lower infiltration of leukemia cells in the liver

spleen and BM of the Cx43+hUCBDSCs+BM group than that in the BM group. Furthermore

increased Cx43 in the BM was observed in the Cx43+hUCBDSCs+BM group than with the BM group. The expression of Cx43 in the bone marrow was enhanced in the Cx43+hUCBDSCs+BM group.

Conclusion

Up-regulation of Cx43 in the hUCBDSCs can induce apoptosis in L615 cells. Combined Cx43 modified hUCBDSCs and hematopoietic stem cells transplantation can promote peripheral WBC and PLT recovery and prevent the relapse of MRD mice.

关键词

Keywords

references

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