Osteoporosis, the most common bone disease, Dabrafenib clinical trial is not only a reduction in bone mass, it is also an increase in marrow adiposity and a reduction in alkaline phosphatase expressing stromal cells [20]. Endosteal fibrosis of secondary hyperparathyroidism is the local accumulation of bone marrow stromal cells at the endosteum [21] and [22]. The fibrosis of fibrous dysplasia of bone (FD) is the local accumulation of stromal cells in an abnormal marrow space [23], is coupled to the loss of adipocytes and of the hematopoietic microenvironment, and also to profound subversion of bone architecture, matrix composition, mineralization,

internal texture and mechanical competence. Vascularity of the bone marrow is profoundly altered in osteoporosis, Paget’s disease, FD, and many more bone diseases. Many more examples could be given illustrating the point that

calling an individual disease a “bone disease” rather than a “bone marrow disease” can be seen as the result of a conventional choice, buy MS-275 or simply of a bias. The introduction of the induced pluripotent stem (iPS) cell technology [24] was saluted with enthusiasm as it conveyed both a reliable technological tool for generating pluripotent cells and theoretically any differentiated lineage, and relief from a heated “ethical” controversy, while illustrating the extraordinary notion that less than a handful these of genes could reprogram an adult cell into pluripotency. Shortly thereafter, the value of iPS

cells as tools for modeling disease became widely appreciated [25], and currently predominates over the still immature use of iPS cells for direct replacement of diseased tissues. The use of iPS cells for disease modeling encompasses investigative as well as directly applicative avenues: the generation of patient-specific diseased and differentiated cell types, in which to seek disease mechanisms, but also a tool for high-throughput drug screening. iPS cells have been used to model rare diseases such as Fibrodysplasia Ossificans Progressiva [26] and metatropic dysplasia [27], revealing altered patterns of cartilaginous differentiation through the use, notably, of assays in fact developed for the study of postnatal stem cells. However, the notion that skeletal diseases could be modeled through stem cells precedes the development of the iPS cell technology. Based on the recognition that obvious changes in the bone marrow stroma occur in FD, Bianco et al. [28] hypothesized that heterotopic transplantation of stromal cells from the abnormal marrow of FD patients could recapitulate in vivo the abnormal architecture of FD bone and bone marrow. This provided evidence that a human non-neoplastic disease could be transferred to immunocompromised mice, and also the first use of stem cells for transferring disease into the mouse.