Targeting gallbladder carcinoma: bone marrow-derived stem cells as therapeutic delivery vehicles of myxoma virus.
- Author:
Mingzhe WENG
1
;
Mingdi ZHANG
1
;
Yiyu QIN
1
;
Wei GONG
1
;
Zhaohui TANG
1
;
Zhiwei QUAN
2
;
Kejin WU
1
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Bone Marrow Cells; cytology; Cell Movement; physiology; Cell Survival; physiology; Female; Gallbladder Neoplasms; therapy; virology; Humans; Immunohistochemistry; Mice; Myxoma virus; pathogenicity; Stem Cells; cytology; physiology; Virus Replication; physiology; Xenograft Model Antitumor Assays
- From: Chinese Medical Journal 2014;127(12):2350-2356
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDGallbladder carcinoma (GBC) has a high mortality rate, requiring synergistic anti-tumor management for effective treatment. The myxoma virus (MYXV) exhibits a modest clinical value through its oncolytic potential and narrow host tropism.
METHODSWe performed viral replication assays, cell viability assays, migration assays, and xenograft tumor models to demonstrate that bone marrow-derived stem cells (BMSCs) may enhance efficiency of intravenous MYXV delivery.
RESULTSWe examined the permissiveness of various GBC cell lines towards MYXV infection and found two supported single and multiple rounds of MYXV replication, leading to an oncolytic effect. Furthermore, we found that BMSCs exhibited tropism for GBC cells within a Matrigel migration system. BMSCs failed to affect the growth of GBC cells, in terms of tumor volume and survival time. Finally, we demonstrated in vivo that intravenous injection of MYXV-infected BMSCs significantly improves the oncolytic effect of MYXV alone, almost to the same extent as intratumoral injection of MYXV.
CONCLUSIONThis study indicates that BMSCs are a promising novel vehicle for MYXV to clinically address gallbladder tumors.