Various Cell Therapy Approaches for Bone Diseases in the Controlled Clinical Trials: A Systematic Review and...

The objective of this review was to answer two critical questions in the cell-based bone defect therapies that were as follows: 1) does cell therapy associate with the increase in the occurrence of adverse events in the patients compared to control groups, 2) does the use of various cell therapy approaches, including More-than Minimal Manipulation (MMM) and Minimal Manipulation (MM), affect the occurrence of adverse events? An electronic literature search was performed in five databases. The controlled clinical trial studies were selected according to the eligibility criteria. Then, they were categorized into MMM and MM approaches, and a meta-analysis of the controlled clinical trials on the occurrence of adverse events was conducted. 23 controlled clinical trials, including 10 MMM (n=341 patients) and 13 MM (n=503 patients) approaches were assessed in this study. Bone defects were oral-maxillofacial defects (7MMM and 8MM), osteonecrosis of the femoral head (1MMM and 5MM), long bone shaft fracture (1MMM), and bone defect during revision total hip arthroplasty (1MMM). Cells were isolated from various tissues such as bone marrow (5MMM and 10MM), the dental pulp (2MMM and 2MM), adipose tissue (2MMM), periosteum (1MMM), and peripheral blood (1MMM). Notably, the adverse events were reported in 37 patients, and 3 patients in MMM and MM approaches, respectively. A meta-analysis demonstrated that there was no association between cell therapy and the occurrence of adverse events. Also, the MMM approach (OR: 1.46) has a higher chance of the occurrence of adverse events compared to the MM approach (OR: 0.71). These results suggested that cell therapy, specifically the MM approach, is safe to improve bone regeneration. Also, future systematic reviews should evaluate the efficacy of these cell therapy approaches.