|Full text PDF:||http://vts.uni-ulm.de/docs/2015/9422/vts_9422_14190.pdf|
Mesenchymal stem cells (MSC) are in focus for regenerative approaches for several decades due to their intrinsic osteogenic differentiation potential. In the present study, it was investigated if systemically administered MSC can support bone formation under non-inflammatory conditions after mechanical loading and after an injury in form of an osteotomy in C567BL/6 mice. Furthermore, it was addressed, if locally implanted human MSC from allogenic and autogenic sources are equally effective in repair of large bone defects in a mouse model with a humanised immune system. The results of the study demonstrated a moderate beneficial effect of systemically administered MSC on fracture healing, shown by a significant increase in bone volume. The injected cells were detected at the newly formed bone in the fracture callus on day 10 and 21 after osteotomy, thus confirming recruitment of the cells. Contrasting the findings in fracture healing, no injected cells were detected in newly formed bone after mechanical loading. Furthermore, no effect of the administered cells on bone formation was detected. In treatment of non-unions and large bone defects, application of allogenic stem cells would solve the issue of limited availability of cells from autogenic sources. The results obtained in this study indicate inferior efficacy of allogenic MSC to regenerate bone in a critical sized bone defect in humanized mice compared to autogenic MSC. In defects treated with autogenic MSC, significantly more bone was evident 35 days after implantation. In conclusion, local application of MSC to regenerate bone seems to be more effective than a systemic approach. Local delivery of the cells leads to an immediate increase of progenitor cell numbers to a super-physiological level and thus more pronounced cell-based effects are likely while an increase in progenitor cells number at the fracture site after systemic administration is unlikely, as cell recruitment remains at a physiological level.