Combination therapy of canine osteosarcoma with canine bone marrow stem cells, bone morphogenetic protein and carboplatin in an in vivo model

Abstract

Osteosarcoma (OSA) is the most common malignant bone cancer in children and dogs. The ther-apeutic protocols adopted for dogs and humans are very similar, involving surgical options suchas amputation. Besides surgical options, radiotherapy and chemotherapy also are adopted. How-ever, hematologic, gastrointestinal and renal toxicity may occur because of chemotherapy treat-ments. Recent study clearly showed that mesenchymal stem cells (MSCs) combined withrecombinant human bone morphogenetic protein (rhBMP-2) may be associated with decreasesof the tumorigenic potential of canine OSA. The aim of this study was to analyse the efficacy ofchemotherapy with carboplatin and rhBMP-2 with MSCs in a canine OSA in vivo model. CanineOSA cells were implanted in mice Balb-c/nude with MSCs, rhBMP-2 and carboplatin. Flow cyto-metry and PCR for markers involved in tumour suppression pathways were analysed. Resultsshowed that the combination of MSCs and rhBMP-2 reduced tumour mass and infiltration ofneoplastic cells in tissues more efficiently than carboplatin alone. Thus it was demonstrated thatthe use of rhBMP-2 and MSCs, in combination with conventional antineoplastic, may be an effi-cient treatment strategy.