Evaluation of Native Mesenchymal Stem Cells from Bone Marrow and Local Tissue in an Atrophic Non-union Model

Introduction It has been reported that cells or growth factors might improve bone regeneration in non-union. However, the intrinsic potential of the non-union tissue to regenerate bone is still unclear, in particular it is not known whether there are progenitor cells within the non-union. Thus, in this study, a clinically relevant model has been developed to investigate the nature of the cells in atrophic non-union tissue and to assess their regenerative potential. Materials and methods Seventeen Wistar rats underwent the procedure to induce an atrophic non-union at the tibial mid shaft by stripping the periosteum and endosteum as well as creating a small (1.0 mm) non-critical gap. The fracture was stabilised with an external fixator. The proliferation ability of bone marrow derived cells and non-union tissue derived cells was determined using colony forming assays. The differentiation potential of non-union tissue derived cells was also investigated. Results Non-critical size defect non-unions were successfully induced in all of the animals. The typical characteristics of atrophic non-unions were demonstrated by radiography, micro-CT and histology. An atrophic non-union stimulated a systemic response in the bone marrow with an increase in bone marrow derived MSCs. In contrast, cells derived from the non-union gap were not able to form colonies. This indicated that the quiescent or inactive cells in the tissue at the atrophic non-union gap could be induced to differentiate under osteogenic and chondrogenic conditions, but not under adipogenic condition. Thus, these cells had the characteristics of osteochondral progenitor cells. Discussion Although there was an increase in the systemic response in the atrophic non-union model, the intrinsic potential of local tissue from the atrophic non-union site was impaired. The cells derived from non-union tissue could be stimulated to differentiate into bone under appropriate conditions. This suggested that there are progenitor cells in atrophic non-union tissue, which have an intrinsic ability to regenerate bone but the microenvironment in the atrophic non-union site might be retarding their function. Consequently, physical or biological agents (such as growth factors or cells) are needed to reactivate the endogenous progenitor cells in order to make them regenerate bone in atrophic non-unions.