Molecular imaging for tracking transplanted embryonic stem cells in the treatment of acute liver injury

doi:10.3969/j.issn.2095-4344.2013.36.016

Abstract

Abstract:

BACKGROUND: Embryonic stem cells have the capacity of multi-differentiation potential, and have been utilized for the therapy of acute liver injury. However, the migration and proliferation of embryonic stem cells after transplantation remains not well characterized.
OBJECTIVE: To track the transplanted embryonic stem cells in repairing acute liver injury by bioluminescence imaging technology.
METHODS: Murine embryonic stem cells (D3) were transducted with a construct composed of firefly luciferase, monomeric red fluorescence protein and herpes simplex virus truncated thymidine kinase triple fusion reporter genes by lentivirus system. Stable D3 embryonic stem cells integrating three report genes were screened. The undifferentiated embryonic stem cells or differentiated embryonic stem cells from the 6-day-old embryoid body were transplanted into acute liver injury model of SV129 mouse through spleen, and the transplanted cells were monitored by bioluminescence imaging technology.
RESULTS AND CONCLUSION: Reverse transcription PCR results showed that the expression level of Oct-4 and Nanog was not affected in embryonic stem cells transducted with triple fusion reporter gene compared with wild-type embryonic stem cells. The migration process of transplanted cells was visualized by bioluminescence imaging technology. Teratomas were found in both triple fusion-embryonic stem cells treatment group and triple fusion-embryoid body cells treatment group at liver, and the teratoma formation could be suppressed by ganciclovir administration because ganciclovir can react with herpes simplex virus truncated thymidine kinase and trigger cell necrosis process. Histological analysis showed that teratomas comprised tissues from all three germ layers. These results demonstrate that triple gene fusion does not affect differentiation potential of embryonic stem cells and it is risky to utilize embryonic stem cells for cell therapy, because it affects repair of liver injury. The therapy strategy requires further improvement and real-time visualizing of embryonic stem cells in vivo is absolutely necessary.

Key words: stem cells, stem cell transplantation, embryonic stem cells, teratoma, genes, transgenic, suicide

CLC Number:

R394.2

Yao Xin-peng, Xu Yang, Zhang Lu, Leng Liang, Su Wei-jun, Wang Li-na, Tong Ling-ling, Li Zong-jin, Kong De-ling. Molecular imaging for tracking transplanted embryonic stem cells in the treatment of acute liver injury[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(36): 6481-6488.

Figures/Tables 6

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