PMID- 36425649
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221126
IS  - 2296-4185 (Print)
IS  - 2296-4185 (Electronic)
IS  - 2296-4185 (Linking)
VI  - 10
DP  - 2022
TI  - The inhibitory effect of human umbilical cord mesenchymal stem cells expressing 
      anti-HAAH scFv-sTRAIL fusion protein on glioma.
PG  - 997799
LID - 10.3389/fbioe.2022.997799 [doi]
LID - 997799
AB  - Glioma is the most common malignant intracranial tumor with low 5-year survival 
      rate. In this study, we constructed a plasmid expressing anti-HAAH single-chain 
      antibody and sTRAIL fusion protein (scFv-sTRAIL), and explored the effects of the 
      double gene modified human umbilical cord mesenchyreal stem cells (hucMSCs) on 
      the growth of glioma in vitro and in vivo. The isolated hucMSCs were identified 
      by detecting the adipogenic differentiation ability and the osteogenic 
      differentiation ability. The phenotypes of hucMSCs were determined by the flow 
      cytometry. The hucMSCs were infected with lentivirus expression scFv-sTRAIL 
      fusion protein. The expression of sTRAIL in hucMSCs were detected by 
      immunofluorescence staining, western blot and ELISA. The tropism of hucMSCs 
      toward U87G cells was assessed by transwell assay. The inhibitory effect of 
      hucMSCs on U87G cells were explored by CCK8 and apoptosis assay. The xenograft 
      tumor was established by subcutaneously injection of U87G cells into the back of 
      mice. The hucMSCs were injected via tail veins. The inhibitory effect of hucMSCs 
      on glioma in vivo was assessed by TUNEL assay. The hucMSCs migrated into the 
      xenograft tumor were revealed by detecting the green fluorescent. The results 
      showed that the scFv-sTRAIL expression did not affect the phenotypes of hucMSCs. 
      The scFv-sTRAIL expression promoted the tropism of hucMSCs toward U87G cells, 
      enhanced the inhibitory effect and tumor killing effect of hucMSCs on U87G cells. 
      The in vivo study showed that hucMSCs expressing scFv-sTRAIL demonstrated 
      significantly higher inhibitory effect and tumor killing effect than hucMSCs 
      expressing sTRAIL. The green fluorescence intensity in the mice injected with 
      hucMSCs expressing scFv-sTRAIL was significantly higher than that injected with 
      hucMSCs expressing sTRAIL. These data suggested that the scFv conferred the 
      targeting effect of hucMSCs tropism towards the xenograft tumor. In conclusion, 
      the hucMSCs expressing scFv-sTRAIL fusion protein gained the capability to target 
      and kill gliomas cells in vitro and in vivo. These findings shed light on a 
      potential therapy for glioma treatment.
CI  - Copyright (c) 2022 Xue, Wang, Ru, Zhang and Yin.
FAU - Xue, Tian
AU  - Xue T
AD  - College of Life Sciences, Northwest University, Xi'an, China.
FAU - Wang, Xiaolin
AU  - Wang X
AD  - Department of Plastic and Burn Surgery, The Second Affiliated Hospital, Air Force 
      Medical University, Xi'an, China.
FAU - Ru, Jing
AU  - Ru J
AD  - CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical 
      Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.
FAU - Zhang, Lixing
AU  - Zhang L
AD  - CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical 
      Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.
FAU - Yin, Huancai
AU  - Yin H
AD  - CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical 
      Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20221108
PL  - Switzerland
TA  - Front Bioeng Biotechnol
JT  - Frontiers in bioengineering and biotechnology
JID - 101632513
PMC - PMC9679793
OTO - NOTNLM
OT  - glioma
OT  - human aspartyl-(asparaginyl)-beta-hydroxylase
OT  - human umbilical cord mesenchyreal stem cells
OT  - single-chain antibody (scFv)
OT  - tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/11/26 06:00
MHDA- 2022/11/26 06:01
PMCR- 2022/01/01
CRDT- 2022/11/25 02:50
PHST- 2022/07/19 00:00 [received]
PHST- 2022/10/26 00:00 [accepted]
PHST- 2022/11/25 02:50 [entrez]
PHST- 2022/11/26 06:00 [pubmed]
PHST- 2022/11/26 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 997799 [pii]
AID - 10.3389/fbioe.2022.997799 [doi]
PST - epublish
SO  - Front Bioeng Biotechnol. 2022 Nov 8;10:997799. doi: 10.3389/fbioe.2022.997799. 
      eCollection 2022.