Amniotic fluid stem cells in a bone microenvironment: driving host angiogenic response.

The repair of skeletal defects remains a substantial economic and biomedical burden. The extra-embryonic fetal stem cells derived from amniotic fluid (AFSCs) have been used for the treatment of large bone defects, but mechanisms of repair are not clear. Here we studied the potential contribution of human AFSCs to the modeling of an ectopic bone. We found that AFSCs are not osteogenic in vivo, and, compared to bone marrow-derived stromal cells, recruit more host CD31 and VEGF-R2 positive cells. Finally, when AFSCs were co-implanted with human-bone forming cells, a normo-osteosynthesis occurred, the engineered ossicle was hyper-vascularized, but AFSCs were not retrieved in the implant within 2weeks. We concluded that AFSCs do not contribute to the deposition of new bone, but act as a powerful proinflammatory/proangiogenic boost, driving a host response, ending in AFSC clearance and vascularization of the bone environment. In our model, a source of osteocommitted cells, capable to engraft and proliferate in vivo, is needed in order to engineer bone. The angio-attractant properties of AFSCs could be exploited in strategies of endogenous cell homing to actively recruit host progenitors into a predefined anatomic location for in situ bone tissue regeneration.