Cell therapy by autologous bone marrow-derived mononuclear cells (BMC) for large bone defect repair: Phase-II clinical trial

Large bone defects remain a major challenge in trauma and orthopedic surgery. Autologous and allogeneic bone are used to repair these defects but are fraught with issues like donor site morbidity, reduced biological capacity, limited availability of autologous bone, immunogenicity or loosening of alloplastic implants and extended surgical times. Bone tissue engineering is an attractive alternative that could minimize or eliminate these limitations or costly complications. Cell based therapy with extensively cultured stem cells (mesenchymal stem cells, MSC and endothelial progenitor cells, EPC) in a large-sized segmental defect could provide preclinically improved vascularization and new bone formation. But these methods are afflicted with disadvantages like long duration of cell culture, increased risk for genetic alterations or contamination with pathogens and hence delay of definitive surgery, biological safety issues, high costs and not yet established clinically. In contrast, BMC (bone marrow-derived mononuclear cells) can be harvested and reintroduced to the patient within hours which is more compatible with the clinical requirement for rapid fracture repositioning. In our own preclinical work BMC provided highly beneficial effects on bone healing in an athymic rat model of critical size defects. Marzi et al. has finished currently a phase-I clinical trial of autologous BMC-therapy for proximal humerus fractures. 10 patients were included and it was demontrated that cell therapy using autologous BMC is safe and feasible when seeded onto ß-TCP in situ into a proximal humeral fracture [manuscript in preparation]. The aim of the proposed phase-II clinical trial is to test the Proof of Concept of a cell-based augmentation with preoperatively isolated autologous BMC seeded onto ß-TCP in combination with an angle stable fixation (Philos plate®) for the therapy of proximal humeral fractures.