Cx43 modified human umbilical cord blood-derived stromal cells prevent relapse in minimal residual disease model of mice after hematopoietic stem cells transplantation

Yi Deng; Shijie Yang; Yanhui Jia; Lei Gao; Cheng Zhang; Yao Liu; Weike Si; Xi Zhang

doi:10.16016/j.1000-5404.201610138

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Cx43 modified human umbilical cord blood-derived stromal cells prevent relapse in minimal residual disease model of mice after hematopoietic stem cells transplantation

更新时间：2026-01-09

- Cx43 modified human umbilical cord blood-derived stromal cells prevent relapse in minimal residual disease model of mice after hematopoietic stem cells transplantation
- Journal of Third Military Medical University Vol. 39, Issue 9, Pages: 813-820(2017)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81070388);the General Program of National Natural Science Foundation of China(81270569);the Basic and Frontier Research Program of Chongqing(CSTC2015jcyjBX0077);the Major Project of the "Twelfth Five-year Plan" of Logistic Scientific Research of PLA(AWS14C014)
- DOI：10.16016/j.1000-5404.201610138
  CLC：
- Received：21 October 2016，
  
  Published：15 May 2017
- 稿件说明：
移动端阅览
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：

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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