Menstrual Blood-derived Stem Cells As Delivery Vehicles For Oncolytic Adenovirus Virotherapy For Colorectal Cancer

Colorectal cancer(CRC)is one of the most malignant gastrointestinal cancers,which threats people’s health because the traditional chemotherapy,radiotherapy and surgery cannot play significant roles in increasing survival rate.Virotherapy is a new and effective method in the treatment of cancer,which has been published in many papers.Oncolytic virus is a type of virus which can selectively replicate in and lyse tumor cells without affecting normal cells,therefore triggering anti-tumor immune responses.However,systematic administration of oncolytic virus will result in antivirus immunity which will decrease the effectiveness of virotherapy.The demand for a suitable vector of transporting oncolytic virus into tumor site is in great need.In this study,we take advantage of menstrual blood-derived stem cells(Men SCs)to transfer oncolytic virus in the treatment of CRC.MenSCs is a new type of adult stem cells,which has a larger source,higher proliferation,less ethnic issues and can be obtained more easily comparing to other types of mesenchymal stem cells.In this study,we firstly isolated and cultivated Men SCs from volunteers’ menstrual blood.Then we detected relative cell markers on the surface and explored the possibility and effectiveness of Men SCs acting as a viral vector for the therapy of CRC.In order to increase viral efficiency and decrease cell cytotoxicity,we constructed a chimeric adenovirus by inserting type 11 virus fiber into type 5 virus,which therefore infected cells mainly depending on CD46 receptor.The cell viability and immunophenotyping of Men SCs were not significantly affected afterviral infection.Besides,we demonstrated that Men SCs-CRAd5/F11 can migrate specifically to tumor both in vitro and in vivo.In addition,we explored the therapeutic potential of Men SCs-CRAd5/F11 by conducting CCK8 assay and cell apoptosis assay,which showed the killing effects of Men SCs-CRAd5/F11 on tumor cells.In vivo,we established a tumor model in BALB/c nude mice and transplanted Men SCs-CRAd5/F11 through different administration methods.Results indicated that tumors were significantly prohibited by Men SCs-CRAd5/F11.Thus,it demonstrated the effectiveness of using Men SCs to load CRAd5/F11 for the therapy of CRC.All in all,MenSCs is a kind of potential vectors,which can transport CRAd5/F11 into tumor site and function anti-tumor effects.The way of applying Men SCsCRAd5/F11 in the treatment of CRC provide a support for clinical cancer therapy.