Assessment of ceramic biomaterial effects on the immunological properties of mesenchymal stromal cells employed in advanced therapies for bone regeneration

Bone is among the most frequently transplanted tissue with about 1 million procedures annually in Europe. Despite their considerable disadvantages, allografts and autografts account for more than 80% of total graft volume. Significant growth opportunities exist for synthetic bone grafts in association with mesenchymal stromal cells (MSCs) from autologous or allogeneic sources as alternatives to biological bone grafts in orthopaedic and maxillofacial surgery. Aim of the present project is to assess the immunomodulatory properties of MSCs of different origin, such as bone marrow, adipose tissue and cord blood, in the presence of a novel biomaterial (HA/TCP) used as scaffold for MSC delivery. The association of all MSC types with the biomaterial does not modulate their phenotype, their anti-apoptotic behaviour and immune modulative properties. Gene transcription analysis reveal that the osteoblastic differentiation was induced when MSCs were cultured for up to 21 days in presence of biomaterial, even in absence of inducers such as dexamethasone or bone morphogenetic protein (BMPs). High osteocalcin expression demonstrates that BM-MSCs could differentiate into terminally osteoblasts if treated with BMP-4 and that differentiated BM-MSCs partially loss their immune suppressive behaviour towards T and NK cell proliferation. Overall, this study increases the knowledge on MSC biology and gives pre- clinical data concerning the use of allogeneic MSC in combination with ceramic scaffolds to treat bone defects.