Human mesenchymal stem cells as delivery of osteoprotegerin gene: homing and therapeutic effect for osteosarcoma

• Published in: Drug design, development and therapy development and therapy, 2015-01, Vol.9, p.969-976
• Main Authors: Qiao, Bo, Shui, Wei, Cai, Li, Guo, Shuquan, Jiang, Dianming
• Format: Article
• Language: English
• Subjects: Adenoviruses; Animals; Biocompatibility; Biological effects; Biological treatment; Biomedical materials; Bone cancer; Bone growth; Bone marrow; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Bone Neoplasms - therapy; bone tumor; Bone tumors; Breast cancer; Cancer therapies; Care and treatment; Destruction; Fluorescence; Gene Targeting; Gene therapy; Gene Transfer Techniques; Genes; Homing; Humans; Laboratory animals; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchyme; Metastasis; Methods; Mice; Mice, Nude; Microscopy; Microscopy, Fluorescence; MSC; Neoplasms, Experimental - genetics; Neoplasms, Experimental - pathology; Neoplasms, Experimental - therapy; OPG; Original Research; Osteoprotegerin; Osteoprotegerin - genetics; Osteosarcoma; Osteosarcoma - genetics; Osteosarcoma - pathology; Osteosarcoma - therapy; Penicillin; Prostate; Proteins; Red fluorescent protein; Sarcoma; Stem cell transplantation; Stem cells; therapy; Tumor Cells, Cultured; Tumors
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S77116

Biological treatments have been studied extensively and previous studies have proved that osteoprotegerin (OPG) can inhibit the development and progress of human osteosarcoma. However, the utility of biologic agents for cancer therapy has a short half-life, which can hardly deliver to and function in tumor sites efficiently. Mesenchymal stem cells (MSCs) have the potential to migrate to tumor sites. In this study, MSCs transfected with adenoviruses carrying the OPG gene (MSCs-OPG) were used via the tail vein to treat athymic nude mice (nu/nu) bearing osteosarcoma. In vivo and ex vivo images were used to validate the MSCs homing to tumors. The therapeutic effect for osteosarcoma was evaluated by observations on growth of tumors and bone destruction. The results showed that infected MSCs-OPG labeled with red fluorescent protein (RFP) can migrate to tumor sites and express OPG protein. The treatment by MSCs-OPG reduced the tumor growth and inhibited bone destruction in vivo. All these indicated that MSCs can deliver OPG to tumor sites, which could be a new direction of biological treatment for human osteosarcoma.