Bone Abstracts

Introduction: Conventional therapy of osteosarcoma, a primary malignant bone tumor, includes surgical excision with wide resection, which leads to physical and aesthetic defects. Allografts for reconstruction of bone and joints and adipose tissue autologous grafts for soft tissue defects can be supplemented with mesenchymal stromal/stem cells (MSCs). Additionally MSCs may be used in tumor-targeted cell therapy. However MSCs may have adverse effects on osteosarcoma development, being stromal component of the tumor microenvironment.

Methods: MSC-like cells were derived from the bone marrow of healthy or osteosarcoma patients and from osteosarcoma biopsies (OS-derived stromal cells). After characterization (ability to form clones, surface markers and differentiation potential), MSC-like cells were used to produce conditioned media that were tested on osteocarcoma cells which were grown either in adhesion-condition or in non-adherent spheres, favouring proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. MSC-like cells were co-injected with osteosarcoma (OS) cells in nude mice. Additionally MSCs have been modified to express tumor-necrosis-factor related apoptosis inducing ligand (TRAIL).

Results: MSCs secreted factors activated osteosarcoma cell cycle from G₁ to mitosis phases, but did not promote the transition from quiescent G₀ to G₁ phases. OS-derived stromal cells showed similar immature markers than bone marrow MSCs, but a higher osteogenic differentiation potential, a higher clone-forming potential and a different oxidative metabolism. They had a normal genotype that distinguished them from tumor cells. These stromal cells alone did not induce tumor in immunodeficient mice (SCID). However, when co-injected with OS cells in nude mice, they increased the local tumor development and, for one patient, they increased the metastatic progression to lungs. When TRAIL-expressing MSCs were co-injected with OS cells in nude mice, the tumor development was similar to that observed with OS cells alone, but it was not inhibited by TRAIL expression.

Conclusion: MSC-like cells may be safe in reconstructive surgery following tumor treatment as they did not change the quiescent state of dormant osteosarcoma cells. In contrast, they accelerated cell cycle of proliferating osteosarcoma cells in vitro and in vivo and they did not appear as good candidates for osteosarcoma cell therapy.

Disclosure: The authors declared no competing interests.