Abstract
Since the monumental publication in 1998 by Pittenger et al., mesenchymal stem cells (MSCs) have been a center player of regenerative medicine and now a number of clinical trials using MSCs have been conducted in various fields of tissue regeneration including those of bone. It cannot be denied that due to enthusiastic clinical demanding, clinical application of MSCs has launched with little knowledge concerning the nature of native MSCs. Recent advances, however, have gradually revealed enigmatic biological properties of MSCs, which subsequently requires the reconsideration of minimum criteria of this type of stem cells. Plastic adherence was no more an absolute requirement of MSCs, and there seemed to be CD34+ MSCs. In addition, in vitro multidirectional property does not guarantee such property in vivo. As a more fundamental issue, cell-of-origin of MSC may be not single, and there seemed to be at least ectodermal (neural crest) MSCs and mesoderm (perivascular) MSCs. Accumulation of preclinical and clinical data has also revealed the role of MSCs in bone regeneration. Against to the initial expectation, the role of MSCs as cell sources to participate bone regeneration seemed to be less significant than those as producer of materials to induce bone regeneration by host cells. The later role may open a new venue of regenerative medicine, which may be called cell-free cell therapy. Understanding of these important features and function of MSC will greatly improve the value of MSCs and promote the proper application of these cells in bone repair and regeneration.
