Tumor risk by tissue engineering: cartilaginous differentiation of mesenchymal stem cells reduces tumor growth

Objective: Implantation of autologous chondrocytes (AC) is a promising option for the treatment of cartilage defects, but problems with cell harvesting, dedifferentiation, or the donor age limit the clinical outcome. Mesenchymal stem cells (MSC) gain much interest because of their simple isolation and multipotential differentiation capacity along with their immunosuppressive properties. The latter might introduce tumor manifestation. The influence of undifferentiated and chondrogenically differentiated MSC or AC on tumor growth and metastasis formation was investigated in a murine melanoma model. Methods: Allogeneic melanoma cells and either syngeneic MSC (C3H10T1/2, transduced with enhanced green fluorescent protein gene) or AC were co-injected at a distance of 3 cm into the contra lateral groins of five mice/group, and evaluated macroscopically and histologically after 4 weeks. Results: Undifferentiated MSC migrated to the tumor site and induced strong tumor growth and metastasis formation. Even a vital MSC promoted tumor growth and spreading, but insignificantly without detectable MSC at the tumor site. Chondrogenically differentiated MSC did not migrate and had a significantly lower impact on tumor growth and spreading; AC had no measurable influence on melanoma cells. Conclusions: Our data suggest that differentiation of MSC reduces MSC-dependent promotion of latent tumors and that native AC do not introduce any increased risk of tumor growth. The question of how far MSC should be differentiated prior to clinical application should be addressed in further studies. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.