Role of autologous adipose-derived stem cells in the early phases of the repairing process of critical bone defects : in vivo rabbit study

Bone defect can be provoked by several pathological conditions, like bone tumors, infections, major trauma with bone stock loss. Surgical techniques currently used for treating bone defects may count on different alternatives, each one of them characterized by both specific complications and drawbacks. Nowadays, an ideal alternative is the use of osteoconductive synthetic bone substitutes either alone or in combination with autologous cells able to enhance the regeneration process and thus to provide better results. Adipose-derived stem cells (ASCs), with their great availability and osteogenic potential may represent, in association with specific scaffolds, a novel and efficient approach for bone regeneration. In this study, rabbit ASCs were expanded in culture and used for the regeneration of full-thickness bone defects in the proximal epiphysis of tibia of twelve New Zealand rabbits. Defects were implanted with graft material as follows: untreated (control), empty hydroxyapatite disk, ASCs alone and hydroxyapatite disk seeded with ASCs. Each isolated ASCs population was tested in vitro: they all showed a high proliferation rate and a marked clonogenic ability and osteogenic differentiation potential. Eight weeks after implantation, macroscopic analyses of all the samples showed satisfactory filling of the lesions without any significant differences in term of stiffness between groups treated with or without cells (p>0.05). In both the scaffold-treated groups, a good osteointegration was radiographically observed. Even if HA was not completely reabsorbed, ASCs-loaded HA displayed a higher scaffold resorption than the unloaded ones. Histological analyses showed that the osteogenic abilities of the scaffold-treated defects was greater than those of scaffold–free samples, and in particular new formed bone was more mature and more similar to native bone in presence of ASCs. These results demonstrated that autologous ASCs-hydroxyapatite constructs is a potential treatment for the regeneration of bone defects.