Abstract

Potential of Autologous 3D Adipose Stem Cells Graft for Bone Reconstruction

Denis Dufrane, Professor, Catholic University of Louvain

A three-dimensional (3D) osteogenic graft from autologous adipose mesenchymal stem cells (AMSCs) was assessed for clinical feasibility, safety, and efficacy for long bone non-union reconstruction. AMSC isolation and differentiation into a 3D “bone-like” structure was performed for (i) three patients with bone tumour and (ii) three patients with bone pseudarthrosis. The subcutaneous adipose tissue was procured by a simple aspiration. A mean of 3•7 ± 0•9 months was required to achieve the 3D osteogenic graft as characterized by the presence of osteoblasts and a mineralization phenotype. No native tumour anomalies were found prior to or after osteogenic differentiation of AMSCs. Although AMSC expansion can induce aneuploidies, such as tri- or tetraploidies or clonal trisomy 7 in 6%–20% of cells, the osteogenic differentiation significantly reduced these clonal anomalies. The graft was implanted in the bone defect without any fixation material or scaffold.No acute (<3 months) side effects, such as impaired wound healing, pain, inflammatory reaction, and infection, or long-term side effects (>1 year), such as tumour development, were associated with the graft up to a maximum of 3 years post-transplantation. Rapid bone consolidation was demonstrated after 3 months without reversibility despite the pathophysiological context of congenital pseudarthrosis and chemotherapy. This first human trial demonstrated (i) the reproducibility of obtaining a 3D structure from autologous AMSCs and (ii) the safety and efficacy of this clinical procedure in stringent and extreme conditions. This technology should be tested on a larger scale for indications requiring bone reconstruction.