Mesenchymal stem cells and bone regeneration: current status.

The enhancement of bone regeneration with biological agents including osteogenic growth factors and mesenchymal stem cells (MSCs) is becoming a clinical reality. Many exciting findings have been obtained following MSC implantation in animal models, and the data demonstrating their clinical efficacy in humans are promising. The overwhelming majority of experimental work has been performed with MSCs "amplified"in vitro. The nature of native MSCs in skeletal tissues however, remains poorly understood. This review summarizes recent findings pertaining to the definition and characterisation of MSCs in skeletal tissues and discusses the mechanisms of their actions in regenerating of bone in vivo. In respect to traditional tissue engineering paradigm, we bring together literature showing that the ways MSCs are extracted, expanded and implanted can considerably affect bone formation outcomes. Additionally, we discuss current animal models used in MSC research and highlight recent experiments showing important contribution of the host, and not only donor MSCs, in bone tissue formation. This knowledge provides a platform for novel therapy development for bone regeneration based on pharmacologically manipulated endogenous MSCs.