**Acknowledgements**

osteoporosis is a systemic disease, and the hormone levels and cytokines have changed dramatically, it is still unclear whether the simple local MSC transplantation can improve these changes in the long-term. In addition, the bone marrow homing efficiency of MSCs and the

Osteogenesis imperfecta is a rare congenital bone development disorder characterized by bone fragility, blue sclera, deafness, and joint relaxation. Horwitz et al. reported three cases of OI using allogeneic bone marrow cells [68]. Six months after the implantation, the new bone formation was observed with a reduced frequency of fractures, suggesting that bone marrow cells could be used to treat OI. The further study from the same group with BMSCs transplantation [69], obtained similar results, that is, donor BMSCs survived in 5/6 OI patients' which

Hypophosphatasia is a rare, heritable, metabolic bone disease due to deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase [70]. The disease is characterized by the disturbance of bone and tooth mineralization and reduced serum ALP activity. Tadokoro et al. used allogeneic MSCs obtained from the patient's father for an 8-month-old patient with hypophosphatasia [71], and they observed improved respiratory condition, and de novo bone derived from both donor and patient cells. Similarly, Cahill et al. reported an 8-month-old girl with worsening and life-threatening infantile HPP improved considerably after marrow cell transplantation [72]. More importantly, 4 months after treatment, radiographs demonstrated improved skeletal mineralization. The authors speculated that donor bone fragments and marrow may provide precursor cells for distribution and engraftment in the skeletal microenvironment in HPP patients to form tissue-nonspecific isoenzyme of alkaline phosphatase-

BMSCs are easy to obtain, isolated and amplified, which provide a wide application prospect for the treatment of orthopedic diseases. Here, we briefly reviewed the progressions ions of MSCs in a variety of orthopedic diseases. Many studies have demonstrated the safety and efficacy of autologous bone marrow MSCs transplantation in animal models as well as in human clinical trials. However, there are still some issues to be solved, such as the reference standards of BMSCs, the regulatory mechanism of proliferation and differentiation of BMSCs, the time, route of administration, and dosages of the transplant. With the further BMSCs

long-term survival of MSCs are still uncertain.

218 Stromal Cells - Structure, Function, and Therapeutic Implications

significantly improved the clinical symptoms of these patients.

replete osteoblasts that can improve mineralization.

researches, we believe that these problems will be solved soon.

**9. MSCs in genetic diseases**

**9.1. Osteogenesis imperfecta (OI)**

**9.2. Hypophosphatasia (HPP)**

**10. Conclusions**

We appreciate the help from many members of the Kessler lab. LK was supported in part by national natural science foundation of China (81472087) and natural science foundation of Anhui province (1508085MC45).
