Potent antitumor efficacy of human dental pulp stem cells armed with YSCH-01 oncolytic adenovirus.

BACKGROUND: Systemic administration of oncolytic adenovirus for cancer therapy is still a challenge. Mesenchymal stem cells as cell carriers have gained increasing attention in drug delivery due to their excellent tumor tropism, immunosuppressive modulatory effects, and paracrine effects. However, the potential of human dental pulp stem cells (hDPSCs) loaded with oncolytic adenovirus for cancer biotherapy has not been investigated yet. METHODS: The stemness of hDPSCs was characterized by FACS analysis and Alizarin red staining, Oil Red O staining, and immunofluorescence assays. The biological fitness of hDPSCs loaded with oncolytic adenovirus YSCH-01 was confirmed by virus infection with different dosages and cell viability CCK-8 assays. Additionally, the expression of CAR receptor in hDPSCs was detected by qPCR assay. Tumor tropism of hDPSC loaded with YSCH-01 in vitro and in vivo was investigated by Transwell assays and living tumor-bearing mice imaging technology and immunohistochemistry, Panoramic scanning of frozen section slices assay analysis. Furthermore, the antitumor efficacy was observed through the different routes of YSCH-01/hPDSCs administration in SW780 and SCC152 xenograft models. The direct tumor cell-killing effect of YSCH-01/hDPSCs in the co-culture system was studied, and the supernatant of YSCH-01/hDPSCs inhibited cell growth was further analyzed by CCK-8 assays. RESULTS: hDPSCs were found to be susceptible to infection by a novel oncolytic adenovirus named YSCH-01 and were capable of transporting this virus to tumor sites at 1000 VP/cell infectious dosage in vitro and in vivo. Moreover, it was discovered that intraperitoneal injection of hDPSCs loaded with oncolytic adenovirus YSCH-01 exhibited potential anti-tumor effects in both SW780 and SCC152 xenograft models. The crucial role played by the supernatant secretome derived from hDPSCs loaded with YSCH-01 significantly exerted a specific anti-tumor effect without toxicity for normal cells, in both an active oncolytic virus and an exogenous protein-independent manner. Furthermore, the use of hDPSCs as a cell carrier significantly reduced the required dosage of virus delivery in vivo compared to other methods. CONCLUSIONS: These findings highlight the promising clinical potential of hDPSCs as a novel cell carrier in the field of oncolytic virus-based anti-cancer therapy.

[The effect of core binding factor alpha1 on transcriptional regulation of mouse dentin sialophosphoprotein].

PURPOSE: To investigate the effect of core binding factor alpha1 (cbfalpha1) on transcriptional regulation of mouse dentin sialophosphoprotein (DSPP) gene. METHODS: The MDPC-23 cells and the segment of nt -2475bp to +53bp were chosen. After co-transfected, the MDPC-23 cells were measured for luciferase activity using the dual luciferase reporter assay system. The results were analyzed by SPSS10.0 software package. RESULTS: In MDPC-23 cells, the luciferase activity was significantly low in the group of co-transfected with pGL3-Enhancer-2.6K and pcDNA3-cbalpha1 than the group of pGL3-Enhancer-2.6K and pcDNA3 (P < 0.01). CONCLUSION: Cbfalpha1 can reduce the activity of DSPP promoter including the segment of nt-2475bp to +53bp in MDPC-23 cells. This suggests that cbfalpha1 can transcriptionally regulate the expression of DSPP. Supported by National Natural Science Foundation of China (Grant No.30271418).