Safety and Efficacy of Embryonic Stem Cell Microenvironment in a Leukemia Mouse Model

自杀基因 生物 胚胎干细胞 骨髓 移植 白血病 体内 癌症研究 肿瘤微环境 遗传增强 免疫学 干细胞 免疫系统 细胞生物学 基因 医学 内科学 生物技术 生物化学
作者
Chenjing Zhou,Zheqian Huang,Panlong Li,Weiqiang Li,Ying Liu,Chaoyang Li,Zhao Liu,Xiaoran Wang,Wan Park,Zhichong Wang
出处
期刊:Stem Cells and Development [Mary Ann Liebert]
卷期号:23 (15): 1741-1754 被引量:8
标识
DOI:10.1089/scd.2013.0585
摘要

The embryonic stem cell (ESC) microenvironment can promote the proliferation of terminal cells and reduce the invasiveness of tumor cells. However, implanting ESCs directly in vivo can result in tumorigenicity, immune rejection after differentiation, and graft-versus-host reaction. Therefore, safety is very important in the clinical application of ESCs. We injected ESCs modified with a suicide gene into a leukemia mouse model through peripheral blood to observe the treatment effectiveness. In addition, according to the pre-test, we set the time point of differentiation after transplantation and then activated the suicide gene to kill the ESCs that we had initially implanted, hoping to avoid the risks mentioned earlier. Our results indicated that the body weight and survival rates of mice treated with an ESC microenvironment increased, and leukemic cells in peripheral blood and bone marrow decreased compared with untreated mice. There was no obvious teratoma in mice that received ESC therapy and induced the suicide gene at the proper time during the observation period, while an apparent teratoma was observed in the lungs of mice which received ESC therapy and never induced the suicide gene. Therefore, the ESC microenvironment can promote self-healing of the in vivo microenvironment. Inducing the suicide gene at the appropriate time can reduce or even avoid tumorigenicity and immune rejection after transplantation of ESCs in vivo and improve the safety of their clinical application.
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