The research of brain glioma therapy for nude mouse using transgenic human umbilical cord mesenchymal stem cells overexpressing TRAIL
10.13303/j.cjbt.issn.1004-549x.2021.06.001
- VernacularTitle:过表达TRAIL转基因人脐带间充质干细胞治疗裸鼠脑胶质瘤的研究
- Author:
Wencui SUN
1
;
Danying YI
1
;
Kejing WU
2
;
Yonggang ZHANG
1
;
Mowen LAI
1
;
Qiongxiu ZHOU
1
;
Feng MA
1
;
Yongjun CHEN
2
;
Shaoxian LIU
2
;
Bo CHEN
1
Author Information
1. Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College ( CAMS & PUMC), Chengdu 610052, China
2. Kangjing Biotechnology Co Ltd.
- Publication Type:Journal Article
- Keywords:
tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL);
hUC-MSCs;
U87 MG;
PiggyBac;
transposon;
nude mouse;
animal experiment
- From:
Chinese Journal of Blood Transfusion
2021;34(6):567-573
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】 To explore the establishment methods of transgenic human umbilical cord mesenchymal stem cells (hUC-MSCs) overexpressing tumor necrosis factor(TNF)-related apoptosis-inducing ligand (TRAIL) based on the transposons, and attempt to apply it on the nude mice mode with glioma. 【Methods】 PiggyBac transposon system specially designed by us was used to prepare non-targeting and Her2-targeting hUC-MSCs that can stably express TRAIL through puromycin screening. The glioma cells expressing firefly luciferase (U87MG-LUC) were injected into the skull of the immunodeficient mice (BALB/c-nu/nu) with 1×106 cells per mouse. After 7 days of injection, the mice transplanted with U87MG were detected with a small animal living imager to determine the size and location of the tumors in skull. Then we injected the glioma-transplantation nude mouse with two kinds of transgenic hUC-MSCs expressing TRAIL (named as untarget-TRAIL and target-TRAIL, respectively), or the non-transgenic hUC-MSCs (all 1×106 cells per mouse) or PBS (named as WT-MSCs and PBS for negative control) respectively, and then monitored the changes of tumor signals by a small animal living imager every week for 3~4 weeks. 【Results】 After six passages to expand the cells, the both transgenic cell lines can stably express TRAIL gene. Their ratio of green fluorescent protein (GFP) positive cells can reach 93%-97%, and the positive ratio of their MSC-specific surface markers still maintained normal (CD34+, CD45+, and HLA-DR+ all <0.1%, CD90>99%, CD73>88%, and CD105 >60%). The median survival time (d) of U87MG-transplanted nude mice in the groups of untarget-TRAIL, target-TRAIL, WT-MSCs, and PBS was 41 vs 39 vs 24 vs 23(P<0.05). 【Conclusion】 The transgenic hUC-MSCs overexpressing TRAIL gene can significantly prolong the survival time of nude mice with brain glioma.
