In the second group (4 trials), BMAC is associated with bone substitutes or demineralized bone matrix (DBM); results have been published about one single trial only [85], observing a shorter time to bone union with cells than in the controls. In the third group, 3 trials intend to test percutaneous injection of

expanded MSCs, but the only completed trial is not yet published. In the fourth group, 3 trials address the association of selleckchem expanded MSC and bone matrix or substitute, but the only completed trial has not been published yet. Needless to say that follow-up of these and other trials on the topic will enlighten the future of the field. A major criticism on the available trials are the underreported results, which may reflect lack of protocol adherence, patient heterogeneity in small unicentric trials, confounding

efficacy results in part due to patient or to protocol variability, or others. GSK-3 inhibitor Many of these trials do not offer sufficient information about the cell product to correlate with the results in other trials and many are also impossible to reproduce in other centers due to lack of transparency. However, reliability is particularly challenged by the size and design of the currently available trials. NADPH-cytochrome-c2 reductase Unless large, comparative trials with well-defined cell products are published, evidence on this

therapy will remain controversial or even negative. A strong need of clinical results is required to further progress in cell therapy. Launched trials will hopefully provide this information in the near future. If clinical results are positive, far greater challenges may be raised by the development of more complex tissue engineering techniques, and this may allow the treatment of large bone defects and unsolved situations [86] after appropriate in vivo models confirm the specific solution to submit to trials. A multidisciplinary approach will be required to improve implanted cell survival and to ensure prompt vessel ingrowth into the biomaterial via careful selection of structure and shape, together with addition of cytokines and growth factors. The development of new materials and cell combinations (hydrogel-based, bioceramic-based, or other) that could eventually craft solutions for supplying cells and biomaterials percutaneously is expected in the near future. The immunosuppressive properties of MSCs may allow the transplantation of allogeneic MSCs in various orthopedic conditions, with the establishment of cell banks for regenerative medicine. Early trials evaluating allogeneic MSCs in delayed unions are already under way.