**9. MSCs in genetic diseases**

### **9.1. Osteogenesis imperfecta (OI)**

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 significantly improved the clinical symptoms of these patients.

### **9.2. Hypophosphatasia (HPP)**

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 phosphatasereplete osteoblasts that can improve mineralization.
